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  1. Effect of haematological alterations on thalassaemia investigation in HIV-1-infected Thai patients receiving antiretroviral therapy.

    PubMed

    Pornprasert, S; Leechanachai, P; Klinbuayaem, V; Leenasirimakul, P; Sukunthamala, K; Thunjai, B; Phusua, A; Saetung, R; Sanguansermsri, T

    2008-10-01

    To evaluate the effect of haematological alterations resulting from antiretroviral therapy (ART) on the diagnosis of thalassaemia carriers in HIV-1-infected Thai patients. Complete blood cell counts, osmotic fragility (OF) test and haemoglobin (Hb)-A(2) values were measured in blood samples of 52 antiretroviral-treated and 14 untreated HIV-1-infected patients. Data were analysed according to thalassaemia type and ART. Sixteen patients carried at least one of the investigated thalassaemia types and most of them (87.5%) received ART. Their red cell indices [mean corpuscular Hb (MCH), mean corpuscular Hb concentration (MCHC) and red blood cell distribution width (RDW)], OF test and Hb-A(2) values were observed within the critical criteria of each thalassaemia type. Normocytic red cells were observed in alpha-thalassaemia and Hb-E trait. Among HIV-1-infected patients who are non-thalassaemia carriers, higher values of Hb-A(2), MCH, macrocytosis and lower red cell counts were observed in the treated group. Values of RDW, MCHC and OF test for treated and untreated groups were in the normal range. Five treated patients had Hb-A(2) values within the critical criteria of beta-thalassaemia carriers but beta-thalassaemia gene mutations were not observed by polymerase chain reaction analysis. ART can alter many haematological figures. Therefore, diagnosis of thalassaemia should be evaluated carefully in combination with those parameters.

  2. Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

  3. Epstein-Barr virus DNA loads in adult human immunodeficiency virus type 1-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Ling, Paul D.; Vilchez, Regis A.; Keitel, Wendy A.; Poston, David G.; Peng, Rong Sheng; White, Zoe S.; Visnegarwala, Fehmida; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) infection are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoma. However, little is known of the EBV DNA loads in patients receiving highly active antiretroviral therapy (HAART). Using a real-time quantitative polymerase chain reaction assay, we demonstrated that significantly more HIV-1-infected patients receiving HAART than HIV-1-uninfected volunteers had detectable EBV DNA in blood (57 [81%] of 70 vs. 11 [16%] of 68 patients; P=.001) and saliva (55 [79%] of 68 vs. 37 [54%] of 68 patients; P=.002). The mean EBV loads in blood and saliva samples were also higher in HIV-1-infected patients than in HIV-1-uninfected volunteers (P=.001). The frequency of EBV detection in blood was associated with lower CD4+ cell counts (P=.03) among HIV-1-infected individuals, although no differences were observed in the EBV DNA loads in blood or saliva samples in the HIV-1-infected group. Additional studies are needed to determine whether EBV-specific CD4+ and CD8+ cells play a role in the pathogenesis of EBV in HIV-1-infected patients receiving HAART.

  4. No Effect of Raltegravir Intensification on Viral Replication Markers in the Blood of HIV-1-infected Patients Receiving Antiretroviral Therapy

    PubMed Central

    Gandhi, Rajesh T.; Coombs, Robert W.; Chan, Ellen S.; Bosch, Ronald J.; Zheng, Lu; Margolis, David M.; Read, Sarah; Kallungal, Beatrice; Chang, Ming; Goecker, Erin A.; Wiegand, Ann; Kearney, Mary; Jacobson, Jeffrey M.; D'Aquila, Richard; Lederman, Michael M.; Mellors, John W.; Eron, Joseph J.

    2011-01-01

    Background Controversy continues regarding the extent of ongoing viral replication in HIV-1-infected patients on effective antiretroviral therapy (ART). Adding an additional potent agent, such as raltegravir, to effective ART in patients with low-level residual viremia may reveal whether there is ongoing HIV-1 replication. Methods We previously reported the outcome of a randomized, placebo-controlled study of raltegravir intensification in patients on ART with HIV-1 RNA <50 copies/mL that showed no effect on residual viremia measured by single copy assay (SCA). We now report the effects of raltegravir intensification in that trial on other potential measures of ongoing HIV-1 replication: 2-LTR HIV-1 circles, total cellular HIV-1 DNA and T cell activation. Results Of 50 patients tested, 12 (24%) had 2-LTR-circles detected at baseline. Patients who were 2-LTR-positive had higher plasma HIV-1 RNA and HIV-1 DNA levels than 2-LTR-negative individuals. At week 12 of raltegravir intensification, there was no change from baseline in 2-LTR circles, in total HIV-1 DNA or in the ratio of 2-LTR circles to total HIV-1 DNA. There was also no change in markers of T cell activation. Conclusions In HIV-1-infected individuals on effective antiretroviral therapy, we find no evidence of ongoing viral replication in the blood that is suppressible by raltegravir intensification. The results imply that raltegravir intensification alone will not eradicate HIV-1 infection. PMID:22083073

  5. Effectiveness, safety, durability and immune recovery in a retrospective, multicentre, observational cohort of ART-experienced, HIV-1-infected patients receiving maraviroc.

    PubMed

    Dentone, C; Sterrantino, G; Signori, A; Cenderello, G; Guerra, M; De Leo, P; Bartolacci, V; Mantia, E; Orofino, G; Giacomini, M; Bruzzone, B; Francisci, D; Di Biagio, A

    2017-10-01

    The aim of this retrospective, multicentre, observational study was to assess the durability, safety, immune recovery and effectiveness on viral suppression of antiretroviral therapy (ART) in a maraviroc (MVC)-based cohort. We collected clinical, demographical, immunological and virological parameters of adult HIV patients who were infected by CCR5-tropic virus and started an ART regimen containing MVC from 2005 to 2012. We created a longitudinal mixed model to assess the change over time of data. We enrolled 126 drug-experienced patients; the median duration of MVC treatment was 25 months. The probability of stopping ART at one year was 13.3%, and at three years was 27.3%. Statistically significant changes were observed for CD4+ cell count increase ( p < 0.001), HIV-RNA decrease ( p < 0.001) and total cholesterol decrease ( p = 0.005). Ninety-four patients (79.7%) had CD4 ≥ 200 cells/mm(3) at baseline while nine of them reached this threshold at nine months (7.6%), 17 (13%) after nine months and six (5%) remained below 200 cells/mm(3) at the end of the study. Overall, 114 patients (90.5%) achieved an HIV-RNA ≤ 50 cp/ml. A majority of patients maintained CD4 cell counts of ≥ 200 cells/mm(3) and achieved an undetectable HIV viral load within three months. MVC-containing regimens are safe and appear to be a feasible therapeutic option for ART.

  6. Modifying Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients.

    PubMed

    Collins, Sean E; Grant, Philip M; Shafer, Robert W

    2016-01-01

    HIV-1-infected patients with suppressed plasma viral loads often require changes to their antiretroviral (ARV) therapy to manage drug toxicity and intolerance, to improve adherence, and to avoid drug interactions. In patients who have never experienced virologic failure while receiving ARV therapy and who have no evidence of drug resistance, switching to any of the acceptable US Department of Health and Human Services first-line therapies is expected to maintain virologic suppression. However, in virologically suppressed patients with a history of virologic failure or drug resistance, it can be more challenging to change therapy while still maintaining virologic suppression. In these patients, it may be difficult to know whether the discontinuation of one of the ARVs in a suppressive regimen constitutes the removal of a key regimen component that will not be adequately supplanted by one or more substituted ARVs. In this article, we review many of the clinical scenarios requiring ARV therapy modification in patients with stable virologic suppression and outline the strategies for modifying therapy while maintaining long-term virologic suppression.

  7. Serum IgD behaviour in HIV-1 infected patients.

    PubMed

    Raiteri, R; Albonico, M; Deiana, R; Marietti, G; Sinicco, A

    1991-01-01

    From September 1987 to February 1990, repeated tests were performed in 325 HIV-1 infected subjects at different clinical stages using a radial immunodiffusion method to determine serum IgD behaviour in HIV-1 infection. Four patients had acute HIV-1 infection, 72 asymptomatic infection, 163 PGL, 49 ARC and 37 AIDS. During the study, 57 seropositive patients developed AIDS. The correlation between serum IgD and the clinical stage of HIV-1 infection, CD4+ and CD8+ lymphocyte levels, CD4+/CD8+ ratio, HIV-1 (p24) antigenemia and reactivity to core proteins, IgG, IgA, IgM isotypes and serum beta 2-microglobulin concentration. A significant correlation was noted between HIV-1 (p24) antigenemia, the disappearance of the antibodies reactivity to core proteins and IgD levels in ARC patients. A progressive increase of serum IgD before the occurrence of the symptomatic stage of HIV-1 infection was observed in HIV-1 infected patients who developed AIDS.

  8. Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART.

    PubMed

    Bekele, Yonas; Amu, Sylvie; Bobosha, Kidist; Lantto, Rebecka; Nilsson, Anna; Endale, Birtukan; Gebre, Meseret; Aseffa, Abraham; Rethi, Bence; Howe, Rawleigh; Chiodi, Francesca

    2015-07-01

    T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied.The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretroviral therapy (ART) and age-matched controls. Flow cytometry was used to characterize the frequency of Tfh cells and B cell subsets. Cytokine expression was measured after in vitro activation of Tfh cells.A reduced frequency of memory Tfh cells (P < 0.001) was identified in HIV-1-infected children and, on these cells, a reduced expression of programmed death-1 (PD-1) and inducible T cell costimulator (ICOS) (P < 0.001 and P < 0.01). Upon activation, the capacity of Tfh cells to express IL-4, an important cytokine for B cell function, was impaired in HIV-1-infected children.B cell subpopulations in HIV-1-infected children displayed significant differences from the control group: the frequency of resting memory (RM) B cells was reduced (P < 0.01) whereas the frequency of exhausted memory B cells increased (P < 0.001). Interestingly, the decline of RM cells correlated with the reduction of memory Tfh cells (P = 0.02).Our study shows that function and phenotype of Tfh cells, pivotal cells for establishment of adaptive B cell responses, are impaired during HIV-1 infection in children. A consistent reduction of memory Tfh cells is associated with declined frequencies of RM B cells, creating a novel link between dysfunctional features of these cell types, major players in establishment of humoral immunity.

  9. Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART

    PubMed Central

    Bekele, Yonas; Amu, Sylvie; Bobosha, Kidist; Lantto, Rebecka; Nilsson, Anna; Endale, Birtukan; Gebre, Meseret; Aseffa, Abraham; Rethi, Bence; Howe, Rawleigh; Chiodi, Francesca

    2015-01-01

    Abstract T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied. The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretroviral therapy (ART) and age-matched controls. Flow cytometry was used to characterize the frequency of Tfh cells and B cell subsets. Cytokine expression was measured after in vitro activation of Tfh cells. A reduced frequency of memory Tfh cells (P < 0.001) was identified in HIV-1-infected children and, on these cells, a reduced expression of programmed death-1 (PD-1) and inducible T cell costimulator (ICOS) (P < 0.001 and P < 0.01). Upon activation, the capacity of Tfh cells to express IL-4, an important cytokine for B cell function, was impaired in HIV-1-infected children. B cell subpopulations in HIV-1-infected children displayed significant differences from the control group: the frequency of resting memory (RM) B cells was reduced (P < 0.01) whereas the frequency of exhausted memory B cells increased (P < 0.001). Interestingly, the decline of RM cells correlated with the reduction of memory Tfh cells (P = 0.02). Our study shows that function and phenotype of Tfh cells, pivotal cells for establishment of adaptive B cell responses, are impaired during HIV-1 infection in children. A consistent reduction of memory Tfh cells is associated with declined frequencies of RM B cells, creating a novel link between dysfunctional features of these cell types, major players in establishment of humoral immunity. PMID:26166114

  10. Serum total antioxidant capacity status of HTLV-1 infected patients.

    PubMed

    Shomali, S; Avval, F Zahedi; Boostani, R; Jarahi, L; Youssefi, M

    2015-06-01

    Many aspects of the pathogenesis of Human T-cell lymphotropic virus type 1 (HTLV-1) still need further elucidations. Previous studies have indicated that oxidative stress occurs during infection with the other retrovirus, human immunodeficiency virus 1 (HIV-1). Similar results have been observed in some other chronic viral infections including hepatitis B (HBV) and hepatitis C (HCV). In order to reveal possible oxidative stress in HTLV-1-infected patients, we evaluated serum total antioxidant capacity (TAC) as an indicator of oxidative stress in these patients. Forty-four HTLV-1-seropositive individuals were included in this study, consisting of 12 symptomatic and 32 asymptomatic (carrier) cases. Controls consisted of 36 apparently healthy, HTLV-1-, HIV- and hepatitis-seronegative individuals. All symptomatic patients had HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Serum TAC levels in patients and healthy individuals were measured using a quantitative TAC assay. The antioxidant capacity in HTLV-1-seropositive cases was significantly reduced compared to control group (P = 0.001). In addition, TAC was lower in patients with more than 5 years history of HAM/TSP compared to those with ≤5 years duration of the myelopathy (P = 0.03). Our results show a depletion of TAC during HTLV-1 infection, which intensifies along with the disease progress. This finding indicates a role of the oxidative stress in pathogenesis of HTLV-1. These results may prompt further research to evaluate any possible therapeutic effect of antioxidant dietary supplements for HTLV-1 infected individuals.

  11. Alterations in the Fecal Microbiota of Patients with HIV-1 Infection: An Observational Study in A Chinese Population

    PubMed Central

    Ling, Zongxin; Jin, Changzhong; Xie, Tiansheng; Cheng, Yiwen; Li, Lanjuan; Wu, Nanping

    2016-01-01

    The available evidence suggests that alterations in gut microbiota may be tightly linked to the increase in microbial translocation and systemic inflammation in patients with human immunodeficiency virus 1 (HIV-1) infection. We profiled the fecal microbiota as a proxy of gut microbiota by parallel barcoded 454-pyrosequencing in 67 HIV-1-infected patients (32 receiving highly active antiretroviral therapy [HAART] and 35 HAART naïve) and 16 healthy controls from a Chinese population. We showed that α-diversity indices did not differ significantly between the healthy control and HIV-1-infected patients. The ratio of Firmicutes/Bacteroidetes increased significantly in HIV-1-infected patients. Several key bacterial phylotypes, including Prevotella, were prevalent in HIV-1-infected patients; whereas Phascolarctobacterium, Clostridium XIVb, Dialister and Megamonas were significantly correlated with systemic inflammatory cytokines. After short-term, effective HAART, the viral loads of HIV-1 were reduced; however, the diversity and composition of the fecal microbiota were not completely restored. and the dysbiosis remained among HIV-1-infected subjects undergoing HAART. Our detailed analysis demonstrated that dysbiosis of fecal microbiota might play an active role in HIV-1 infection. Thus, new insights may be provided into therapeutics that target the microbiota to attenuate the progression of HIV disease and to reduce the risk of gut-linked disease in HIV-1-infected patients. PMID:27477587

  12. T follicular helper cells and antibody response to Hepatitis B virus vaccine in HIV-1 infected children receiving ART.

    PubMed

    Bekele, Yonas; Yibeltal, Desalegn; Bobosha, Kidist; Andargie, Temesgen E; Lemma, Mahlet; Gebre, Meseret; Mekonnen, Eyasu; Habtewold, Abiy; Nilsson, Anna; Aseffa, Abraham; Howe, Rawleigh; Chiodi, Francesca

    2017-08-21

    HBV vaccine has 95% efficacy in children to prevent HBV infection and related cancer. We conducted a prospective study in HIV-1 infected children receiving ART (n = 49) and controls (n = 63) to assess humoral and cellular responses to HBV vaccine provided with three doses under an accelerated schedule of 4 weeks apart. At 1 month post-vaccination all children, except 4 HIV-1 infected, displayed protective antibody (ab) titers to HBV vaccine; ab titers were lower in infected children (P < 0.0001). Ab titers decreased (P < 0.0001) in both HIV-1 infected and control children at 6 months. The frequency of circulating Tfh (cTFh) cells was 20.3% for controls and 20.8% for infected children prior to vaccination and remained comparable post-vaccination. Cytokine expression by cTfh cells upon activation with HBV antigen was comparable in the two groups at baseline and 1 month post-vaccination. Higher plasma levels (P < 0.0001) of CXCL13 were found in infected children which correlated with cTfh cell frequency at baseline. In conclusion, a lower ab response to HBV vaccine was measured in HIV-1 infected children. The frequency and activation profile of cTfh cells was comparable in infected children and controls suggesting that cells other than Tfh cells are responsible for impaired ab response to HBV vaccine.

  13. Dolutegravir for the treatment of adult patients with HIV-1 infection.

    PubMed

    Wu, Gary; Abraham, Teena; Saad, Nasser

    2014-05-01

    Dolutegravir, is a second generation integrase inhibitor that had recently received United States Food and Drug Administration and European Commission approval for the treatment of adult patients with HIV-1 infection. Dolutegravir provides distinct advantages compared with first generation integrase inhibitors. Unlike raltegravir, dolutegravir can be given once daily for patients who are antiretroviral treatment naïve. Once-a-day dolutegravir dosing also does not require a pharmacokinetic booster like elvitegravir which minimizes the drug-drug interaction potential of dolutegravir. In Phase III clinical trials, dolutegravir-containing regimens have demonstrated either non-inferiority or superiority to current first line agents such as raltegravir, darunavir/ritonavir, and efavirenz containing regimens. Moreover, dolutegravir may be effective for patients with a history of raltegravir and/or elvitegravir resistance. Dolutegravir will likely play a major role in the management of patients with HIV-1 infection, and will be aided when coformulation with abacavir/lamivudine as a single pill, once-daily regimen is available.

  14. Increased proviral load in HTLV-1-infected patients with rheumatoid arthritis or connective tissue disease.

    PubMed

    Yakova, Maria; Lézin, Agnès; Dantin, Fabienne; Lagathu, Gisèle; Olindo, Stéphane; Jean-Baptiste, Georges; Arfi, Serge; Césaire, Raymond

    2005-02-01

    Human T-lymphotropic virus type 1 (HTLV-1) proviral load is related to the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has also been shown to be elevated in the peripheral blood in HTLV-1-infected patients with uveitis or alveolitis. Increased proliferation of HTLV-1-infected cells in, or migration of such cells into, the central nervous system is also seen in HAM/TSP. In the present study, we evaluated the proviral load in a cohort of HTLV-1-infected patients with arthritic conditions. HTLV-1 proviral load in the peripheral blood from 12 patients with RA and 6 patients with connective tissue disease was significantly higher than that in matched asymptomatic HTLV-1 carriers, but similar to that in matched HAM/TSP controls. HAM/TSP was seen in one-third of the HTLV-1-infected patients with RA or connective tissue disease, but did not account for the higher proviral load compared to the asymptomatic carrier group. The proviral load was increased in the synovial fluid and tissue from an HTLV-1-infected patient with RA, the values suggesting that the majority of infiltrated cells were HTLV-1-infected. In the peripheral blood from HTLV-1-infected patients with RA or connective tissue disease, HTLV-1 proviral load correlated with the percentages of memory CD4+ T cells and activated T cells, and these percentages were shown to be markedly higher in the synovial fluid than in the peripheral blood in an HTLV-1-infected patient with RA. These biological findings are consistent with a role of the retrovirus in the development of arthritis in HTLV-1-infected patients. A high level of HTLV-1-infected lymphocytes in the peripheral blood and their accumulation in situ might play a central role in the pathogenesis of HTLV-1-associated inflammatory disorders. Alternatively, the autoimmune arthritis, its etiological factors or treatments might secondarily enhance HTLV-1 proviral load.

  15. Warfarin-induced skin necrosis in HIV-1-infected patients with tuberculosis and venous thrombosis.

    PubMed

    Bhaijee, F; Wainwright, H; Meintjes, G; Wilkinson, R J; Todd, G; De Vries, E; Pepper, D J

    2010-06-01

    At the turn of the century, only 300 cases of warfarin-induced skin necrosis (WISN) had been reported. WISN is a rare but potentially fatal complication of warfarin therapy. There are no published reports of WISN occurring in patients with HIV-1 infection or tuberculosis (TB). We retrospectively reviewed cases of WISN presenting from April 2005 to July 2008 at a referral hospital in Cape Town, South Africa. Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%). All 6 cases occurred in HIV-1-infected women (median age 30 years, range 27 - 42) with microbiologically confirmed TB and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis 49 cells/microl, interquartile range 23 - 170). Of the 3 patients receiving combination antiretroviral therapy, 2 had TB-IRIS (immune reconstitution inflammatory syndrome). The median interval from initiation of antituberculosis treatment to venous thrombosis was 37 days (range 0 - 150). The median duration of parallel heparin and warfarin therapy was 2 days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 6.2 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs. Four of 6 WISN sites were secondarily infected with drug-resistant nosocomial bacteria (methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae) 17 - 37 days after WISN onset. In 4 patients, the median interval from WISN onset to death was 43 days (range 25 - 45). One of the 2 patients who survived underwent bilateral mastectomies and extensive skin grafting at a specialist centre. This is one of the largest case series of WISN. We report a novel clinical entity: WISN in HIV-1 infected patients with TB and venous thrombosis. The

  16. Penetration of dapsone into pulmonary lining fluid of human immunodeficiency virus type 1-infected patients.

    PubMed Central

    Cruciani, M; Gatti, G; Mengoli, C; Cazzadori, A; Lazzarini, L; Miletich, F; Graziani, M S; Malena, M; Bassetti, D

    1997-01-01

    We studied the penetration of dapsone into the epithelial lining fluid (ELF) of sixteen human immunodeficiency virus type 1-infected patients who had received the drug at a dose of 100 mg twice weekly as primary prophylaxis for Pneumocystis carinii pneumonia. Bronchoscopy, bronchoalveolar lavage (BAL), and venipuncture were performed for each patient at a specific time after administration of the last dose of dapsone. Dapsone concentrations in plasma and BAL were determined by high-performance liquid chromatography. The apparent volume of ELF recovered by BAL was determined by using urea as an endogenous marker. The mean concentrations of dapsone in ELF at 2 h (five patients), 4 h (three patients), 12 h (two patients), 24 h (three patients), and 48 h (three patients) were 0.95, 0.70, 1.55, 0.23, and 0.45 mg/liter, respectively, while concentrations in plasma were 1.23, 0.79, 1.31, 0.83, and 0.18 mg/liter, respectively. Dapsone concentrations in ELF were 76, 79, 115, 65, and 291% of those observed in plasma at the same times, respectively. These data show that dapsone is well distributed into ELF and that a twice-weekly 100-mg prophylactic regimen results in sustained concentrations in this compartment. PMID:9145873

  17. Seroprevalence and vaccination coverage of vaccine-preventable diseases in perinatally HIV-1-infected patients

    PubMed Central

    Sticchi, Laura; Bruzzone, Bianca; Caligiuri, Patrizia; Rappazzo, Emanuela; Lo Casto, Michele; De Hoffer, Laura; Gustinetti, Giulia; Viscoli, Claudio; Di Biagio, Antonio

    2014-01-01

    Background Even in the era of highly active antiretroviral therapy (HAART), HIV-infected subjects are at higher risk of complications from vaccine-preventable diseases than those uninfected. The current international guidelines strongly recommend that these patients should receive all the routine childhood vaccinations. Although these children represent an appropriate target for immunization, the available data indicate suboptimal coverage rates. Methods To evaluate seroprotection/seropositivity rates and vaccination coverage against the common vaccine-preventable diseases, all patients with vertically transmitted HIV-1 infection who attended San Martino Hospital were enrolled. Blood samples were collected for testing antibodies against diphtheria, tetanus, hepatitis A and B viruses by Enzyme-Linked ImmunoSorbent Assay and polioviruses by microneutralization test. In order to assess immunization coverage, retrospectively was recorded the vaccination history collecting data from Regional Immunization Database. Results A total of 39 perinatally HIV-1 infected patients were included in the study. At the time of serum was obtained, the mean age was 18,1 years (range: 6–28). The median CD4+ T-lymphocyte count was 702 cells/mm3 (2–1476 cells/mm3). Twenty-nine (74.4%) patients were found with HIV RNA load < 50 copies/mL. The proportion of subjects with protective anti-tetanus and anti-HBs were 43.6% and 30.8%, respectively. Seroprotection rates about 20% against rubella and measles were found, less than 20% against all the other antigens investigated. In particular, all patients resulted susceptible to mumps. High immunization rates were observed for polio and HBV (100% and 92.3%, respectively) and suboptimal for diphtheria-tetanus (84.6%). For the other recommended vaccines the rates were generally low. None of the patients received varicella vaccine doses. Conclusions As in the HAART era the vertically acquired HIV infection has become a chronic treatable disease

  18. Absence of primary integrase resistance mutations in HIV type 1-infected patients in Venezuela.

    PubMed

    Rangel, Héctor R; Garzaro, Domingo; Fabbro, Rona; Martinez, Nahir; Ossenkop, John; Torres, Jaime R; Gutiérrez, Cristina R; Pujol, Flor H

    2010-08-01

    The preexistence of mutations to integrase inhibitors in HIV-1-infected Venezuelan patients was evaluated. The integrase region of the HIV-1 genome was amplified by nested-PCR and sequenced in 57 isolates from both naive (n = 24) and treated patients who received protease and/or reverse transcriptase inhibitors (PI and RTI, n = 33), but were never exposed to integrase inhibitors. Only one primary integrase resistance mutation, not conferring drug resistance by itself, was found among these patients, although several minor viral mutations, equally distributed among naive and PI- and RTI-treated patients, were also found. In the limited number of samples, no relation was found among the presence of resistance mutations to PI or RTI and the presence of minor mutations to integrase. The absence of resistance to integrase inhibitors may be related to the recent introduction of these drugs in our country. The availability of in-house assays allows for a more comprehensive surveillance of drug resistance to integrase inhibitors in Venezuela.

  19. Immunological Profile of HTLV-1-Infected Patients Associated with Infectious or Autoimmune Dermatological Disorders

    PubMed Central

    Duarte, Mariana Costa; Araújo, Marcelo Grossi; Campi-Azevedo, Ana Carolina; Teixeira-Carvalho, Andréa; Peruhype-Magalhães, Vanessa; Trindade, Bruno Caetano; dos Santos Dias, Raquel; Martins, Marina Lobato; Carneiro-Proietti, Anna Barbara de Freitas; Guedes, Antônio Carlos; Gonçalves, Denise Utsch; Martins-Filho, Olindo Assis

    2013-01-01

    In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4+HLA-DR+, CD8+ T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection. PMID:23936564

  20. Immunological profile of HTLV-1-infected patients associated with infectious or autoimmune dermatological disorders.

    PubMed

    Coelho-dos-Reis, Jordana Grazziela Alves; Passos, Livia; Duarte, Mariana Costa; Araújo, Marcelo Grossi; Campi-Azevedo, Ana Carolina; Teixeira-Carvalho, Andréa; Peruhype-Magalhães, Vanessa; Trindade, Bruno Caetano; Dos Santos Dias, Raquel; Martins, Marina Lobato; Carneiro-Proietti, Anna Barbara de Freitas; Guedes, Antônio Carlos; Gonçalves, Denise Utsch; Martins-Filho, Olindo Assis

    2013-01-01

    In the present study, the frequency, the activation and the cytokine and chemokine profile of HTLV-1 carriers with or without dermatological lesions were thoroughly described and compared. The results indicated that HTLV-1-infected patients with dermatological lesions have distinct frequency and activation status when compared to asymptomatic carriers. Alterations in the CD4(+)HLA-DR(+), CD8(+) T cell, macrophage-like and NKT subsets as well as in the serum chemokines CCL5, CXCL8, CXCL9 and CXCL10 were observed in the HTLV-1-infected group with skin lesions. Additionally, HTLV-1 carriers with dermatological skin lesions showed more frequently high proviral load as compared to asymptomatic carriers. The elevated proviral load in HTLV-1 patients with infectious skin lesions correlated significantly with TNF-α/IL-10 ratio, while the same significant correlation was found for the IL-12/IL-10 ratio and the high proviral load in HTLV-1-infected patients with autoimmune skin lesions. All in all, these results suggest a distinct and unique immunological profile in the peripheral blood of HTLV-1-infected patients with skin disorders, and the different nature of skin lesion observed in these patients may be an outcome of a distinct unbalance of the systemic inflammatory response upon HTLV-1 infection.

  1. Off-label use of maraviroc in HIV-1-infected paediatric patients in clinical practice.

    PubMed

    Palladino, Claudia; Gómez, María Luisa Navarro; Soler-Palacín, Pere; González-Tomé, María Isabel; De Ory, Santiago J; Espiau, María; Hoyos, Santiago Pérez; León-Leal, Juan Antonio; Méndez, María; Moreno-Pérez, David; Guasch, Claudia Fortuny; Sierra, Antoni Mur; Guruceta, Itziar Pocheville; Guillén, Santiago Moreno; Briz, Verónica

    2015-10-23

    Maraviroc (MVC) is not approved for HIV-1-infected paediatric patients. This is the first assessment of the use of MVC-based salvage therapy in vertically HIV-1-infected paediatric patients in clinical settings. The results suggest that MVC-based salvage therapy is useful in children and adolescents with extensive resistance profile leading to maintained virological suppression in up to 88% of the patients with CCR5-tropic virus. The likelihood of treatment success might increase when MVC is combined with other active drugs.

  2. Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients.

    PubMed

    Martin-Loeches, Ignacio; Díaz, Emili; Vidaur, Loreto; Torres, Antoni; Laborda, Cesar; Granada, Rosa; Bonastre, Juan; Martín, Mar; Insausti, Josu; Arenzana, Angel; Guerrero, Jose Eugenio; Navarrete, Ines; Bermejo-Martin, Jesus; Suarez, David; Rodriguez, Alejandro

    2011-01-01

    There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection.

  3. Pandemic and post-pandemic Influenza A (H1N1) infection in critically ill patients

    PubMed Central

    2011-01-01

    Background There is a vast amount of information published regarding the impact of 2009 pandemic Influenza A (pH1N1) virus infection. However, a comparison of risk factors and outcome during the 2010-2011 post-pandemic period has not been described. Methods A prospective, observational, multi-center study was carried out to evaluate the clinical characteristics and demographics of patients with positive RT-PCR for H1N1 admitted to 148 Spanish intensive care units (ICUs). Data were obtained from the 2009 pandemic and compared to the 2010-2011 post-pandemic period. Results Nine hundred and ninety-seven patients with confirmed An/H1N1 infection were included. Six hundred and forty-eight patients affected by 2009 (pH1N1) virus infection and 349 patients affected by the post-pandemic Influenza (H1N1)v infection period were analyzed. Patients during the post-pandemic period were older, had more chronic comorbid conditions and presented with higher severity scores (Acute Physiology And Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA)) on ICU admission. Patients from the post-pandemic Influenza (H1N1)v infection period received empiric antiviral treatment less frequently and with delayed administration. Mortality was significantly higher in the post-pandemic period. Multivariate analysis confirmed that haematological disease, invasive mechanical ventilation and continuous renal replacement therapy were factors independently associated with worse outcome in the two periods. HIV was the only new variable independently associated with higher ICU mortality during the post-pandemic Influenza (H1N1)v infection period. Conclusion Patients from the post-pandemic Influenza (H1N1)v infection period had an unexpectedly higher mortality rate and showed a trend towards affecting a more vulnerable population, in keeping with more typical seasonal viral infection. PMID:22126648

  4. Increased incidence of hepatocellular carcinoma (HCC) in HIV-1 infected patients.

    PubMed

    Murillas, Javier; Del Río, Manuel; Riera, Melchor; Vaquer, Pedro; Salas, Ana; Leyes, María; Angeles Ribas, M; Peñaranda Vera, María; Villalonga, Concepcion

    2005-04-01

    BACKGROUND: The likely increased incidence of hepatocarcinoma (HCC) in HIV-1 infected patients has not yet been demonstrated. METHODS: We studied all cases of HCC occurring in HIV-1 infected patients in our hospital during the past 15 years. Incidence and survival time were compared with those of the general population in the same area and the same time of the study. RESULTS: We found 6 cases of HCC in a cohort of 2383 HIV-1 infected patients between 1986 and 2001. This is a higher than expected incidence rate of HCC compared with the general population, with a standardized incidence ratio of 13.95. Chronic hepatitis virus infection and alcohol abuse were present in four and two cases, respectively. In one patient, no liver disease was known before the HCC and the surrounding liver was normal in the necropsy study. CONCLUSION: The improved survival of patients on highly active antiretroviral treatment (HAART) and the increasing incidence of end-stage liver disease in these patients caused by chronic hepatitis virus infection and alcohol abuse may be responsible for an increase in the incidence of HCC in HIV-1 infected patients.

  5. Predicting bacteremic pneumonia in HIV-1-infected patients consulting the ED.

    PubMed

    Perelló, Rafael; Miró, Oscar; Marcos, María Angeles; Almela, Manel; Bragulat, Ernest; Sánchez, Miquel; Agustí, Carlos; Miro, José M; Moreno, Asunción

    2010-05-01

    HIV-1-infected patients have higher incidence of community-acquired pneumonia (CAP) and risk of complications. Bacteremia has been associated with a higher risk of complications in such patients. We investigated factors associated with bacteremia in HIV-1-infected patients with CAP presenting at the emergency department. We included HIV-1-infected patients with CAP for 3 years (March 2005-February 2008). Only patients in whom blood cultures were performed were finally included. Clinical data (age; sex; CD4(+) count; serum HIV viral load; previous or current intravenous drug use and antiretroviral treatment; systolic blood pressure; and cardiac and respiratory rates), analytical data (leukocyte count, arterial oxygen content, C-reactive protein value, and urgent Streptococcus pneumoniae and Legionella spp antigen urine detection), and APACHE-II (Acute Physiology and Chronic Health Evaluation) score were compiled. The need for intensive care unit admission, mechanical ventilation, mortality, and for patients finally discharged, duration of admission were retrospectively obtained from the clinical history. A multivariate analysis using logistic regression was performed to find independent predictors of bacteremia. We diagnosed 129 HIV-1-infected patients with CAP. Blood cultures were performed in 118 cases (91%). Bacteremia was present in 28 (24%). Independent predictors of bacteremia were the detection of S pneumoniae antigen in urine (odds ratio, 9.0; 95% confidence interval, 1.9-42.0) and the absence of current antiretroviral treatment (odds ratio, 7.1; 95% confidence interval, 1.4-33.3). In-hospital mortality was higher in patients with bacteremia (15% vs 0%). HIV-1-infected patients with CAP who are not on current antiretroviral therapy and have positive S pneumoniae antigenuria are at increased risk of having bacteremia. Bacteremic patients have a poor outcome. (c) 2010 Elsevier Inc. All rights reserved.

  6. Investigation of emtricitabine-associated skin pigmentation and safety in HIV-1-infected Japanese patients.

    PubMed

    Shirasaka, Takuma; Tadokoro, Taketsugu; Yamamoto, Yasuyuki; Fukutake, Katsuyuki; Kato, Yukihiko; Odawara, Takashi; Nakamura, Tetsuya; Ajisawa, Atsushi; Negishi, Masayoshi

    2011-10-01

    Emtricitabine (FTC) has been reported to cause skin pigmentation (SP), and the incidence of SP associated with FTC varied with ethnicity, with a higher rate in African-American patients (8%). We assessed the incidence of SP in Japanese HIV-1-infected patients receiving combination antiretroviral therapy (cART) with FTC for a period of 48 weeks and confirmed new findings of FTC-associated SP, including pathological characteristics. This was a multicenter, prospective, longitudinal non-randomized study. We evaluated the appearance of SP at 48 weeks as the primary endpoint in 155 Japanese patients, and secondary endpoints included the characteristics of the SP (location, color tone, size, and progression). Six cases (3.9%) of SP occurred at a median of 124 days (range: 7-259 days) within 48 weeks. The SP looked like an isolated dark spot, 1-2 mm in diameter, mainly on the hands and/or feet. The severity of all the SPs was mild. Each SP had disappeared or faded at a median of 112 days (range: 28-315 days) with continued FTC. FTC-associated SP was considered to be lentigo simplex by dermatoscopy and pathological appearance. In summary, the incidence of FTC-associated SP in Japanese patients was 3.9%, and was comparable to the previously reported incidence in Asian patients (4%). FTC-associated SP was not associated with any clinically significant symptoms and has little clinical significance.

  7. Oxidative Imbalance in HIV-1 Infected Patients Treated with Antiretroviral Therapy

    PubMed Central

    Mandas, Antonella; Iorio, Eugenio Luigi; Congiu, Maria Gabriella; Balestrieri, Cinzia; Mereu, Antonello; Cau, Daniela; Dessì, Sandra; Curreli, Nicoletta

    2009-01-01

    It is generally accepted that oxidative stress is involved in HIV infection. However, the role in oxidative balance of Highly Active Antiretroviral Therapy (HAART) is still debated. In our study we assessed serum oxidant and antioxidant levels in an HIV-1-infected population treated with HAART, and compared them with those of untreated HIV-1 patients and HIV-1-negative subjects. The study included 116 HIV-1-infected patients (86 HAART-treated and 30 untreated), and 46 HIV-negative controls. Serum oxidant levels were significantly higher in the HIV-1 treated group as compared to untreated and control groups. In addition, a decrease of serum total antioxidant status was observed in the HIV-1 treated group. To be noted is that patients who rigorously follow antiretroviral therapy (optimal HAART adherence) have significantly higher oxidative status than those who do not closely follow the therapy (poor HAART adherence). Analysis of variance revealed no significant further increase in oxidative status in HIV-1-infected patients taking antiretroviral and other drugs with the exception of psychiatric drugs (e.g. anxiolytics or antidepressants). Taken together, our results indicate that HAART may affect oxidative stress in HIV-1-infected patients and suggest that antiretroviral therapy plays an important role in the synergy of HIV infection and oxidative stress. PMID:19884983

  8. Prevalence of HLA-B*57:01 allele in Argentinean HIV-1 infected patients.

    PubMed

    Moragas, M; Belloso, W H; Baquedano, M S; Gutierrez, M I; Bissio, E; Larriba, J M; Fay, F; Aulicino, P; Gurevich, J M; Yaunguzian, M F; Maldonado, A C; Falistocco, C; Sen, L; Mangano, A

    2015-07-01

    Hypersensitivity reaction to abacavir (ABC hypersensitivity syndrome, AHS) is strongly associated with the presence of the HLA-B*57:01 allele. This study was designed to estimate the prevalence of HLA-B*57:01 allele in Argentinean HIV-1 infected patients. We analyzed the presence of HLA-B*57:01 allele in 1646 HIV-1 infected patients from different regions of Argentina. This allele was detected in 81 patients; most of them corresponded to patients living in the central region of the country. The prevalence of HLA-B*57:01 was 4.9%, similar to other Caucasian populations and higher than other data reported for South American populations. This strongly supports screening for the presence of HLA-B*57:01 in abacavir treatment of HIV-1 in our country. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Psychosocial factors affecting medication adherence among HIV-1 infected adults receiving combination antiretroviral therapy (cART) in Botswana.

    PubMed

    Do, Natalie T; Phiri, Kelesitse; Bussmann, Hermann; Gaolathe, Tendani; Marlink, Richard G; Wester, C William

    2010-06-01

    As increasing numbers of persons are placed on potentially life-saving combination antiretroviral therapy (cART) in sub-Saharan Africa, it is imperative to identify the psychosocial and social factors that may influence antiretroviral (ARV) medication adherence. Using an 87 question survey, the following data were collected from patients on cART in Botswana: demographics, performance (Karnofsky) score, perceived stigma and level of HIV disclosure, attitudes and beliefs concerning HIV/AIDS, substance and/or drug use, depression, and pharmacy and healthcare provider-related factors. Overall adherence rates were determined by patient self-report, institutional adherence, and a culturally modified Morisky scale. Three hundred adult patients were recruited between April and May 2005. The overall cART adherence rate was 81.3% based on 4 day and 1 month patient recall and on clinic attendance for ARV medication refills during the previous 3 months. Adults receiving cART for 1-6 months were the least adherent (77%) followed by those receiving cART for greater than 12 months (79%). Alcohol use, depression, and nondisclosure of positive HIV status to their partner were predictive of poor adherence rates (p value <0.02). A significant proportion (81.3%) of cART-treated adults were adherent to their prescribed treatment, with rates superior to those reported in resource-rich settings. Adherence rates were poorest among those just starting cART, most likely due to the presence of ARV-related toxicity. Adherence was lower among those who have been treated for longer periods of time (greater than 1 year), suggesting complacency, which may become a significant problem, especially among these long-term cART-treated patients who return to improved physical and mental functioning and may be less motivated to adhere to their ARV medications. Healthcare providers should encourage HIV disclosure to "at-risk" partners and provide ongoing counseling and education to help patients

  10. SEROPREVALENCE OF HTLV IN A POPULATION OF HIV1-INFECTED PATIENTS IN MIDWESTERN BRAZIL

    PubMed Central

    KOZLOWSKI, Aline Garcia; de MATOS, Márcia Alves Dias; CARNEIRO, Megmar Aparecida dos Santos; LOPES, Carmen Luci Rodrigues; TELES, Sheila Araújo; VICENTE, Carolina Paulo; MARTINS, Regina Maria Bringel

    2016-01-01

    SUMMARY Human T-cell lymphotropic virus (HTLV) may affect the clinical course of human immunodeficiency virus 1 (HIV1). Both infections are common in endemic areas because these viruses share similar routes of transmission. The aim of this study was to estimate the seroprevalence of HTLV1/2 in a population of HIV1-infected patients in the state of Goiás, Midwestern Brazil. Of the 505 studied patients, four (0.79%) were positive for anti-HTLV1/2 by enzyme-linked immunosorbent assay (ELISA), with HTLV1 infection confirmed by line immunoassay (LIA) and polymerase chain reaction (PCR) in all of the ELISA-positive samples. No cases of HTLV2 infection were observed. The prevalence of HTLV1/HIV1 coinfection was 0.79% (4/505; 95% CI: 0.25-2.16). All the coinfected patients reported sexual risk behaviors and only one reported intravenous drug use. Sequencing of the viral long terminal repeat (LTR) region and phylogenetic analysis revealed that the four HTLV1 isolates belonged to the Transcontinental a subgroup of the Cosmopolitan (1a) subtype, the most frequent subgroup detected in Brazil. This study shows a low prevalence of HTLV1/2 in HIV1-infected patients in Midwestern Brazil. PMID:27828621

  11. The Influence of Coinfection on Mood States in HTLV-1-Infected Patients.

    PubMed

    Gascón, Maria Rita Polo; Capitão, Claudio Garcia; Nogueira-Martins, Maria Cezira Fantini; Casseb, Jorge; Penalva Oliveira, Augusto Cesar

    2012-01-01

    The objective of this study was to discuss the influence of coinfection on mood states (depression and anxiety) in Human T Lymphotropic virus type 1 HTLV-1-infected patients. A cross-sectional study was performed with a sample obtained through a nonprobabilistic technique. A total of 130 patients in treatment at the HTLV Ambulatory of Instituto de Infectologia Emílio Ribas participated in the research, of whom 63 had HAM/TS and 67 were asymptomatic. A sociodemographic survey and the Beck Anxiety and Depression Inventories were used. The results indicated a prevalence of 7.2% for HTLV-1/HIV co-infection, 7.2% for HTLV-1/HCV, and 4.0% for HTLV-1/HIV/HCV. It is possible that the presence of a co-infection causes greater fear and concern about the future than asymptomatic HTLV-1 infection, increasing the observed degree of depression and anxiety.

  12. The Influence of Coinfection on Mood States in HTLV-1-Infected Patients

    PubMed Central

    Gascón, Maria Rita Polo; Capitão, Claudio Garcia; Nogueira-Martins, Maria Cezira Fantini; Casseb, Jorge; Penalva Oliveira, Augusto Cesar

    2012-01-01

    The objective of this study was to discuss the influence of coinfection on mood states (depression and anxiety) in Human T Lymphotropic virus type 1 HTLV-1-infected patients. A cross-sectional study was performed with a sample obtained through a nonprobabilistic technique. A total of 130 patients in treatment at the HTLV Ambulatory of Instituto de Infectologia Emílio Ribas participated in the research, of whom 63 had HAM/TS and 67 were asymptomatic. A sociodemographic survey and the Beck Anxiety and Depression Inventories were used. The results indicated a prevalence of 7.2% for HTLV-1/HIV co-infection, 7.2% for HTLV-1/HCV, and 4.0% for HTLV-1/HIV/HCV. It is possible that the presence of a co-infection causes greater fear and concern about the future than asymptomatic HTLV-1 infection, increasing the observed degree of depression and anxiety. PMID:23738200

  13. Daclatasvir plus Asunaprevir Treatment for Real-World HCV Genotype 1-Infected Patients in Japan

    PubMed Central

    Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Suzuki, Eiichiro; Arai, Makoto; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Background. All-oral combination of direct-acting antivirals could lead to higher sustained virologic response (SVR) in hepatitis C virus (HCV)-infected patients. In the present study, we examined the efficacy and safety of the dual oral treatment with HCV nonstructural protein (NS) 5A inhibitor daclatasvir (DCV) plus HCV NS3/4A inhibitor asunaprevir (ASV) for 24 weeks in real-world HCV genotype 1-infected Japanese individuals. Methods. After screening for HCV NS5A resistance-associated variants (RAVs) by PCR invader assay, a total of 54 Japanese patients infected with HCV genotype 1 treated with DCV plus ASV were retrospectively analyzed. SVR12 was used for evaluation of the virologic response. Results. Of the total 54 patients, 46 patients (85.2%) were treated with DCV plus ASV for 24 weeks and achieved SVR12. The other 8 patients (14.8%) discontinued this treatment before 24 weeks due to adverse events. Of these 8 patients, 5 and 3 patients did and did not achieve SVR12, respectively. Finally, 51 of 54 (94.4%) patients achieved SVR12. Conclusion. Treatment with DCV and ASV after screening for HCV NS5A RAVs by PCR invader assay is effective and safe in the treatment of real-world HCV genotype 1-infected patients in Japan. PMID:27279790

  14. Daclatasvir plus Asunaprevir Treatment for Real-World HCV Genotype 1-Infected Patients in Japan.

    PubMed

    Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Suzuki, Eiichiro; Arai, Makoto; Haga, Yuki; Sasaki, Reina; Wu, Shuang; Nakamoto, Shingo; Imazeki, Fumio; Yokosuka, Osamu

    2016-01-01

    Background. All-oral combination of direct-acting antivirals could lead to higher sustained virologic response (SVR) in hepatitis C virus (HCV)-infected patients. In the present study, we examined the efficacy and safety of the dual oral treatment with HCV nonstructural protein (NS) 5A inhibitor daclatasvir (DCV) plus HCV NS3/4A inhibitor asunaprevir (ASV) for 24 weeks in real-world HCV genotype 1-infected Japanese individuals. Methods. After screening for HCV NS5A resistance-associated variants (RAVs) by PCR invader assay, a total of 54 Japanese patients infected with HCV genotype 1 treated with DCV plus ASV were retrospectively analyzed. SVR12 was used for evaluation of the virologic response. Results. Of the total 54 patients, 46 patients (85.2%) were treated with DCV plus ASV for 24 weeks and achieved SVR12. The other 8 patients (14.8%) discontinued this treatment before 24 weeks due to adverse events. Of these 8 patients, 5 and 3 patients did and did not achieve SVR12, respectively. Finally, 51 of 54 (94.4%) patients achieved SVR12. Conclusion. Treatment with DCV and ASV after screening for HCV NS5A RAVs by PCR invader assay is effective and safe in the treatment of real-world HCV genotype 1-infected patients in Japan.

  15. A Retrospective Cohort Study of Lesion Distribution of HIV-1 Infection Patients With Cryptococcal Meningoencephalitis on MRI

    PubMed Central

    Xia, Shuang; Li, Xueqin; Shi, Yanbin; Liu, Jinxin; Zhang, Mengjie; Gu, Tenghui; Pan, Shinong; Song, Liucun; Xu, Jinsheng; Sun, Yan; Zhao, Qingxia; Lu, Zhiyan; Lu, Puxuan; Li, Hongjun

    2016-01-01

    Abstract The objective of this paper is to correlate the MRI distribution of cryptococcal meningoencephalitis in HIV-1 infection patients with CD4 T cell count and immune reconstitution effect. A large retrospective cohort study of HIV patients from multi-HIV centers in China was studied to demonstrate the MRI distribution of cryptococcal meningoencephalitis and its correlation with the different immune status. The consecutive clinical and neuroimaging data of 55 HIV-1-infected patients with cryptococcal meningoencephalitis collected at multi-HIV centers in China during the years of 2011 to 2014 was retrospectively analyzed. The enrolled patients were divided into 2 groups based on the distribution of lesions. One group of patients had their lesions at the central brain (group 1, n = 34) and the other group of patients had their lesions at the superficial brain (group 2, n = 21). We explored their MRI characterization of brain. In addition, we also compared their CD4 T cell counts and immune reconstitution effects between the 2 groups based on the imaging findings. No statistical difference was found in terms of age and gender between the 2 groups. The medians of CD4 T cell counts were 11.67 cells/mm3 (3.00–52.00 cells/mm3) in group 1 and 42.00 cells/mm3 (10.00–252.00 cells/mm3) in group 2. Statistical difference of CD4 T cell count was found between the 2 groups (P = 0.023). Thirteen patients in group 1 (13/34) and 12 patients in group 2 (12/21) received highly active antiretroviral treatment (HAART). Patients of group 2 received HAART therapy more frequently than patients of group 1 (P = 0.021). Central and superficial brain lesions detected by MR imaging in HIV-1-infected patients with cryptococcal meningoencephalitis are in correlation with the host immunity and HAART therapy. PMID:26871791

  16. PPARgamma Pro12Ala polymorphism in HIV-1-infected patients with HAART-related lipodystrophy.

    PubMed

    Saumoy, Maria; Veloso, Sergi; Alonso-Villaverde, Carlos; Domingo, Pere; Chacón, Matilde R; Miranda, Merce; Aragonès, Gerard; Gutiérrez, Maria Mar; Viladés, Consuelo; Peraire, Joaquim; Sirvent, Joan-Josep; López-Dupla, Miguel; Aguilar, Carmen; Richart, Cristóbal; Vidal, Francesc

    2009-09-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) is involved in obesity and in some components of the metabolic syndrome in unselected population. To determine whether PPARgamma genetic variants are associated with the risk of developing lipodystrophy and its associated metabolic disturbances in HIV-1-infected patients treated with HAART and to assess PPARgamma mRNA expression in subcutaneous adipose tissue (SAT). The study group comprised 278 patients infected with HIV-1 and treated with antiretroviral drugs (139 with lipodystrophy and 139 without) and 105 uninfected controls (UC). The PPARgamma Pro12Ala (C%>G) single nucleotide polymorphism (SNP) was assessed using PCR-RFLPs on white cell DNA. PPARgamma mRNA expression in SAT was assessed in 38 patients (25 with lipodystrophy and 13 without) and in 21 UC by real-time PCR. Statistical analysis was based on Student's T tests, Chi(2) tests, Spearman's correlations tests and logistic regression tests. PPARgamma Pro12Ala genotype distribution and allele frequencies were non-significantly different between both HIV-1-infected categories, lipodystrophy vs non-lipodystrophy (p=0.9 and p=0.87, respectively). Lipodystrophic patients harbouring the rare X/Ala genotype (Ala/Ala plus Pro/Ala) had significantly greater plasma total and LDL cholesterol levels compared with carriers of the common Pro/Pro genotype (p=0.029 and p=0.016, respectively) at univariate analyses. At multivariate analyses these associations were no longer significant. There was a near-significant decreased SAT PPARgamma mRNA expression in patients with lipodystrophy compared to UC (p=0.054). PPARgamma Pro12Ala SNP has no effect on the risk of developing lipodystrophy in HIV-1-infected patients treated with HAART. PPARgamma mRNA SAT expression appears decreased in lipodystrophy.

  17. Deletion, insertion and stop codon mutations in vif genes of HIV-1 infecting slow progressor patients.

    PubMed

    Rangel, Héctor Rafael; Garzaro, Domingo; Rodríguez, Anny Karely; Ramírez, Alvaro Hernán; Ameli, Gladys; Del Rosario Gutiérrez, Cristina; Pujol, Flor Helene

    2009-08-30

    Variable progression towards AIDS has been described and has been related to viral and host factors. Around 10% of the HIV-1 infected patients are slow progressors (SP), not presenting with AIDS disease signs even after more than 10 years of infection. Viral gene defects have been associated with the disease progression but more studies are still needed. The sequence of vif and nef were analyzed for HIV-1 infecting 14 SP and 46 normal progressors (NP) patients. Co-circulation of a strain carrying vif deleted gene with the wild type strain was detected in an SP patient with more than 10 years of infection. Other mutations (insertion in aa 63 in one strain, two premature stop codons in another one) were found in viruses infecting two other patients. Except for the SP8 strain, which exhibited a premature stop codon in nef, no gross deletions or insertions were observed in nef genes of both NPs and SPs strains analyzed. Different kind of mutation: deletion, insertion and stop codon, were detected in 3/14 samples from SP, with co-circulation of a 195 bp vif deletion virus with a wild type in one of these patients. Although vif defects do not seem to be a frequent feature in SPs, this study illustrates the importance of analysing this gene, in addition to the multiple factors associated with the long-term non progression to AIDS.

  18. Effectiveness of Simeprevir Plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients With HCV Genotype 1 Infection.

    PubMed

    Sulkowski, Mark S; Vargas, Hugo E; Di Bisceglie, Adrian M; Kuo, Alexander; Reddy, K Rajender; Lim, Joseph K; Morelli, Giuseppe; Darling, Jama M; Feld, Jordan J; Brown, Robert S; Frazier, Lynn M; Stewart, Thomas G; Fried, Michael W; Nelson, David R; Jacobson, Ira M

    2016-02-01

    The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET--a prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, there were 836 patients with HCV genotype 1 infection who began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most patients had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as the level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment--a 2-week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. The overall SVR rate was 84% (675 of 802 patients, 95% confidence interval, 81%-87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. In a large prospective observational cohort study, a 12-week regimen of simeprevir plus sofosbuvir was associated with

  19. Effectiveness of Simeprevir plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients with HCV Genotype 1 Infection

    PubMed Central

    Sulkowski, MS; Vargas, HE; Di Bisceglie, AM; Kuo, PA; Reddy, KR; Lim, JK; Morelli, G; Darling, JM; Feld, JJ; Brown, RS; Frazier, LM; Stewart, TG; Fried, MW; Nelson, DR; Jacobson, IM

    2015-01-01

    Background & Aims The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. Methods We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET—a prospective, observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, 836 patients with HCV genotype 1 infection began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment—a 2 week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. Results The overall rate of SVR rate was 84% (675/802 patients, 95% CI: 81–87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. Conclusions In a large, prospective observational cohort study, a 12 week regimen of simeprevir plus sofosbuvir was

  20. Non-AIDS-defining events among HIV-1-infected adults receiving combination antiretroviral therapy in resource-replete versus resource-limited urban setting

    PubMed Central

    Wester, C. William; Koethe, John R.; Shepherd, Bryan E.; Stinnette, Samuel E.; Rebeiro, Peter F.; Kipp, Aaron M.; Hong, Hwanhee; Bussmann, Hermann; Gaolathe, Tendani; McGowan, Catherine C.; Sterling, Timothy R.; Marlink, Richard G.

    2011-01-01

    Objective To compare incidence and distribution of non-AIDS-defining events (NADEs) among HIV-1-infected adults receiving combination antiretroviral therapy (cART) in urban sub-Saharan African versus United States settings. Design Retrospective cohort analysis of clinical trial and observational data. Methods Compared crude and standardized (to US cohort by age and sex) NADE rates from two urban adult HIV-infected cART-initiating populations: a clinical trial cohort in Gaborone, Botswana (Botswana) and an observational cohort in Nashville, Tennessee (USA). Results Crude NADE incidence rates were similar: 10.0 [95% confidence interval 6.3–15.9] per 1000 person-years in Botswana versus 12.4 [8.4–18.4] per 1000 person-years in the United States. However, after standardizing to an older, predominantly male US population, the overall NADE incidence rates were higher in Botswana [18.7 (8.3–33.1) per 1000 person-years]. Standardized rates differed most for cardiovascular events (8.4 versus 5.0 per 1000 person-years) and non-AIDS-defining malignancies (8.0 versus 0.5 per 1000 person-years) – both higher in Botswana. Conversely, hepatic NADE rates were higher in the United States (4.0 versus 0.0 per 1000 person-years), whereas renal NADE rates [3.0 per 1000 person-years (United States) versus 2.4 per 1000 person-years (Botswana)] were comparable. Conclusion Crude NADE incidence rates were similar between cART-treated patients in a US observational cohort and a sub-Saharan African clinical trial. However, when standardized to the US cohort, overall NADE rates were higher in Botswana. NADEs appear to be a significant problem in our sub-Saharan African setting, and the monitoring, prevention, and treatment of NADEs should be a critical component of care in resource-limited settings. PMID:21572309

  1. Prevalence of anxiety, depression and quality of life in HTLV-1 infected patients.

    PubMed

    Gascón, Maria Rita Polo; Capitão, Claudio Garcia; Casseb, Jorge; Nogueira-Martins, Maria Cezira Fantini; Smid, Jerusa; Oliveira, Augusto César Penalva de

    2011-01-01

    The HAM/TSP caused by HTLV-1 infection usually affects patients to disabling states, and sometimes can lead them to paraplegia presenting symptoms of depression and anxiety, impacting on quality of life. The purpose of this study was to evaluate the frequency of depression and anxiety and its impact on quality of life in HTLV-1-infected TSP/HAM patients. This was a cross-sectional study including 67 asymptomatic (control group) and 63 with TSP/HAM subjects. The instruments used were a demographic questionnaire, scales for anxiety and depression diagnosis (BDI and BAI), questionnaire for the assessment of Quality of Life of the World Health Organization (WHOQOL-Brief) and neurological scale to measure the disability level (Osame's Disability Status Scale). All patients had HTLV-I diagnosis by serological and molecular approaches, monitored at Instituto de Infectologia Emílio Ribas from May 2008 to July 2009. Data were analyzed statistically by frequencies, the Mann-Whitney test and the Spearman correlation test. Data among groups were analyzed and correlated with functional and severity aspects. The results showed that patients with HAM/TSP compared to asymptomatic carriers had higher rates of depression (p < 0.001) and anxiety (p < 0.001), and impairment on quality of life in the areas of: dissatisfaction with health (p < 0.001), physical (p < 0.001) and the environment (p = 0.003). The main factors that correlated with levels of depression and anxiety and the domains of the WHOQOL-brief were: education, family income and social class. A well conducted evaluation and counseling may help in treatment, for a better quality of life of these patients.

  2. Stimulation of the primary anti-HIV antibody response by IFN-{alpha} in patients with acute HIV-1 infection

    PubMed Central

    Adalid-Peralta, Laura; Godot, Véronique; Colin, Céline; Krzysiek, Roman; Tran, Thi; Poignard, Pascal; Venet, Alain; Hosmalin, Anne; Lebon, Pierre; Rouzioux, Christine; Chêne, Geneviève; Emilie, Dominique

    2008-01-01

    Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-α2b. Patients with acute HIV-1 infection were randomized to receive anti-retroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-α2b (Group B, n=30). Emergence of anti-HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-α2b treatment stimulated the production of anti-HIV antibodies. On Week 32, 19 weeks after the last IFN-α2b administration, there were 8.5 (6.5–10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0–10.0) bands in Group A (P=0.054), and band intensities were stronger in Group B (P<0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-α2b treatment also increased circulating concentrations of the B cell-activating factor of the TNF family (P<0.001) and ex vivo production of IL-12 (P<0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P<0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies. PMID:18182457

  3. Stimulation of the primary anti-HIV antibody response by IFN-alpha in patients with acute HIV-1 infection.

    PubMed

    Adalid-Peralta, Laura; Godot, Véronique; Colin, Céline; Krzysiek, Roman; Tran, Thi; Poignard, Pascal; Venet, Alain; Hosmalin, Anne; Lebon, Pierre; Rouzioux, Christine; Chene, Genevieve; Emilie, Dominique

    2008-04-01

    Type I IFNs are needed for the production of antiviral antibodies in mice; whether they also stimulate primary antibody responses in vivo during human viral infections is unknown. This was assessed in patients acutely infected with HIV-1 and treated with IFN-alpha2b. Patients with acute HIV-1 infection were randomized to receive antiretroviral therapy alone (Group A, n=60) or combined for 14 weeks with pegylated-IFN-alpha2b (Group B, n=30). Emergence of anti-HIV antibodies was monitored during 32 weeks by Western blot (WB) analyses of serum samples. IFN-alpha2b treatment stimulated the production of anti-HIV antibodies. On Week 32, 19 weeks after the last IFN-alpha2b administration, there were 8.5 (6.5-10.0) HIV WB bands (median, interquartile range) in Group B and 7.0 (5.0-10.0) bands in Group A (P=0.054), and band intensities were stronger in Group B (P<0.05 for p18, p24, p34, p40, and p55 HIV antigens). IFN-alpha2b treatment also increased circulating concentrations of the B cell-activating factor of the TNF family (P<0.001) and ex vivo production of IL-12 (P<0.05), reflecting its effect on innate immune cells. Withdrawal of antiretroviral treatment on Week 36 resulted in a lower rebound of HIV replication in Group B than in Group A (P<0.05). Therefore, type I IFNs stimulate the emerging anti-HIV immune response in patients with acute HIV-1 infection, resulting in an improved control of HIV replication. Type I IFNs are thus critical in the development of efficient antiviral immune responses in humans, including the production of antiviral antibodies.

  4. Dysfunctional phenotypes of CD4+ and CD8+ T cells are comparable in patients initiating ART during early or chronic HIV-1 infection

    PubMed Central

    Amu, Sylvie; Lantto Graham, Rebecka; Bekele, Yonas; Nasi, Aikaterini; Bengtsson, Carina; Rethi, Bence; Sorial, Sam; Meini, Genny; Zazzi, Maurizio; Hejdeman, Bo; Chiodi, Francesca

    2016-01-01

    Abstract Early initiation of antiretroviral therapy (ART) is becoming a common clinical practice according to current guidelines recommending treatment to all HIV-1-infected patients. However, it is not known whether ART initiated during the early phase of infection prevents the establishment of abnormal phenotypic features previously reported in CD4+ and CD8+T cells during chronic HIV-1 infection. In this cross-sectional study, blood specimens were obtained from 17 HIV-1-infected patients who began ART treatment shortly after infection (early ART [EA]), 17 age-matched HIV-1-infected patients who started ART during chronic phase of infection (late ART [LA]), and 25 age-matched non-HIV-1-infected controls. At collection of specimens, patients in EA and LA groups had received ART for comparable periods of time. Total HIV-1 DNA was measured in white blood cells by quantitative PCR. The concentration of 9 inflammatory parameters and 1 marker of fibrosis, including sCD14 and β-2 microglobulin, was measured in plasma. Furthermore, expression of markers of abnormal immune activation (human leukocyte antigen - antigen D related [HLA-DR] and CD38), exhaustion (programmed death 1, CD28, CD57) and terminal differentiation (CD127) was measured on CD4+ and CD8+T cells. T-cell proliferation was measured through Ki67 expression. The copies of total HIV-1 DNA in blood were significantly lower (P = 0.009) in EA compared with that in LA group. Only the expression of HLA-DR on naïve CD4+ T cells distinguished EA from LA, whereas expression of 3 surface markers distinguished T-cell populations of HIV-1-infected patients from controls. These included HLA-DR distinguishing CD4+ T cells from EA compared with controls, and also CD38 and CD127 on CD4+ and CD8+ T cells, respectively, distinguishing both groups of patients from controls. The sCD14 levels were significantly higher in EA patients, and β-2 microglobulin levels were higher in LA group compared with that in controls. Our

  5. Dysfunctional phenotypes of CD4+ and CD8+ T cells are comparable in patients initiating ART during early or chronic HIV-1 infection.

    PubMed

    Amu, Sylvie; Lantto Graham, Rebecka; Bekele, Yonas; Nasi, Aikaterini; Bengtsson, Carina; Rethi, Bence; Sorial, Sam; Meini, Genny; Zazzi, Maurizio; Hejdeman, Bo; Chiodi, Francesca

    2016-06-01

    Early initiation of antiretroviral therapy (ART) is becoming a common clinical practice according to current guidelines recommending treatment to all HIV-1-infected patients. However, it is not known whether ART initiated during the early phase of infection prevents the establishment of abnormal phenotypic features previously reported in CD4+ and CD8+T cells during chronic HIV-1 infection. In this cross-sectional study, blood specimens were obtained from 17 HIV-1-infected patients who began ART treatment shortly after infection (early ART [EA]), 17 age-matched HIV-1-infected patients who started ART during chronic phase of infection (late ART [LA]), and 25 age-matched non-HIV-1-infected controls. At collection of specimens, patients in EA and LA groups had received ART for comparable periods of time. Total HIV-1 DNA was measured in white blood cells by quantitative PCR. The concentration of 9 inflammatory parameters and 1 marker of fibrosis, including sCD14 and β-2 microglobulin, was measured in plasma. Furthermore, expression of markers of abnormal immune activation (human leukocyte antigen - antigen D related [HLA-DR] and CD38), exhaustion (programmed death 1, CD28, CD57) and terminal differentiation (CD127) was measured on CD4+ and CD8+T cells. T-cell proliferation was measured through Ki67 expression. The copies of total HIV-1 DNA in blood were significantly lower (P = 0.009) in EA compared with that in LA group. Only the expression of HLA-DR on naïve CD4+ T cells distinguished EA from LA, whereas expression of 3 surface markers distinguished T-cell populations of HIV-1-infected patients from controls. These included HLA-DR distinguishing CD4+ T cells from EA compared with controls, and also CD38 and CD127 on CD4+ and CD8+ T cells, respectively, distinguishing both groups of patients from controls. The sCD14 levels were significantly higher in EA patients, and β-2 microglobulin levels were higher in LA group compared with that in controls. Our results

  6. Characteristics and determinants of T-cell phenotype normalization in HIV-1-infected individuals receiving long-term antiretroviral therapy.

    PubMed

    Ndumbi, P; Gillis, J; Raboud, J; Cooper, C; Hogg, R S; Montaner, J S G; Burchell, A N; Loutfy, M R; Machouf, N; Klein, M B; Tsoukas, C

    2014-03-01

    Although combination antiretroviral therapy (cART) can restore CD4 T-cell numbers in HIV infection, alterations in T-cell regulation and homeostasis persist. We assessed the incidence and predictors of reversing these alterations with cART. ART-naïve adults (n = 4459) followed within the Canadian Observational Cohort and exhibiting an abnormal T-cell phenotype (TCP) prior to cART initiation were studied. Abnormal TCP was defined as having (1) a low CD4 T-cell count (< 532 cells/μL), (2) lost T-cell homeostasis (CD3 < 65% or > 85%) or (3) CD4:CD8 ratio dysregulation (ratio < 1.2). To thoroughly evaluate the TCP, CD4 and CD8 T-cell percentages and absolute counts were also analysed for a median duration of 3.14 years [interquartile range (IQR) 1.48-5.47 years]. Predictors of TCP normalization were assessed using adjusted Cox proportional hazards models. At baseline, 96% of pateints had CD4 depletion, 32% had lost homeostasis and 99% exhibited ratio dysregulation. With treatment, a third of patients had normalized CD4 T-cell counts, but only 85 individuals (2%) had normalized their TCP. In a multivariable model adjusted for age, measurement frequency and baseline regimen, higher baseline CD4 T-cell counts and time-dependent viral suppression independently predicted TCP normalization [hazard ratio (HR) for baseline CD4 T-cell count = 1.42 (1.31-1.54) per 100 cells/μL increase; P ≤ 0.0001; HR for time-dependent suppressed viral load = 3.69 (1.58-8.61); P-value ≤ 0.01]. Despite effective cART, complete TCP recovery occurred in very few individuals and was associated with baseline CD4 T-cell count and viral load suppression. HIV-induced alterations of the TCP are incompletely reversed by long-term ART. © 2013 British HIV Association.

  7. High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo

    PubMed Central

    Salou, Mounerou; Dagnra, Anoumou Y; Butel, Christelle; Vidal, Nicole; Serrano, Laetitia; Takassi, Elom; Konou, Abla A; Houndenou, Spero; Dapam, Nina; Singo-Tokofaï, Assetina; Pitche, Palokinam; Atakouma, Yao; Prince-David, Mireille; Delaporte, Eric; Peeters, Martine

    2016-01-01

    Introduction Antiretroviral treatment (ART) has been scaled up over the last decade but compared to adults, children living with HIV are less likely to receive ART. Moreover, children and adolescents are more vulnerable than adults to virological failure (VF) and emergence of drug resistance. In this study we determined virological outcome in perinatally HIV-1-infected children and adolescents receiving ART in Togo. Methods HIV viral load (VL) testing was consecutively proposed to all children and adolescents who were on ART for at least 12 months when attending HIV healthcare services for their routine follow-up visit (June to September 2014). Plasma HIV-1 VL was measured using the m2000 RealTime HIV-1 assay (Abbott Molecular, Des Plaines, IL, USA). Genotypic drug resistance was done for all samples with VL>1000 copies/ml. Results and discussion Among 283 perinatally HIV-1-infected children and adolescents included, 167 (59%) were adolescents and 116 (41%) were children. The median duration on ART was 48 months (interquartile range: 28 to 68 months). For 228 (80.6%), the current ART combination consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) (zidovudine and lamivudine) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) (nevirapine or efavirenz). Only 28 (9.9%) were on a protease inhibitor (PI)-based regimen. VL was below the detection limit (i.e. 40 copies/ml) for 102 (36%), between 40 and 1000 copies/ml for 35 (12.4%) and above 1000 copies/ml for 146 (51.6%). Genotypic drug-resistance testing was successful for 125/146 (85.6%); 110/125 (88.0%) were resistant to both NRTIs and NNRTIs, 1/125 (0.8%) to NRTIs only, 4/125 (3.2%) to NNRTIs only and three harboured viruses resistant to reverse transcriptase and PIs. Overall, 86% (108/125) of children and adolescents experiencing VF and successfully genotyped, corresponding thus to at least 38% of the study population, had either no effective ART or had only a single effective drug in

  8. A Retrospective Cohort Study of Lesion Distribution of HIV-1 Infection Patients With Cryptococcal Meningoencephalitis on MRI: Correlation With Immunity and Immune Reconstitution.

    PubMed

    Xia, Shuang; Li, Xueqin; Shi, Yanbin; Liu, Jinxin; Zhang, Mengjie; Gu, Tenghui; Pan, Shinong; Song, Liucun; Xu, Jinsheng; Sun, Yan; Zhao, Qingxia; Lu, Zhiyan; Lu, Puxuan; Li, Hongjun

    2016-02-01

    The objective of this paper is to correlate the MRI distribution of cryptococcal meningoencephalitis in HIV-1 infection patients with CD4 T cell count and immune reconstitution effect.A large retrospective cohort study of HIV patients from multi-HIV centers in China was studied to demonstrate the MRI distribution of cryptococcal meningoencephalitis and its correlation with the different immune status.The consecutive clinical and neuroimaging data of 55 HIV-1-infected patients with cryptococcal meningoencephalitis collected at multi-HIV centers in China during the years of 2011 to 2014 was retrospectively analyzed. The enrolled patients were divided into 2 groups based on the distribution of lesions. One group of patients had their lesions at the central brain (group 1, n = 34) and the other group of patients had their lesions at the superficial brain (group 2, n = 21). We explored their MRI characterization of brain. In addition, we also compared their CD4 T cell counts and immune reconstitution effects between the 2 groups based on the imaging findings.No statistical difference was found in terms of age and gender between the 2 groups. The medians of CD4 T cell counts were 11.67 cells/mm (3.00-52.00 cells/mm) in group 1 and 42.00 cells/mm (10.00-252.00 cells/mm) in group 2. Statistical difference of CD4 T cell count was found between the 2 groups (P = 0.023). Thirteen patients in group 1 (13/34) and 12 patients in group 2 (12/21) received highly active antiretroviral treatment (HAART). Patients of group 2 received HAART therapy more frequently than patients of group 1 (P = 0.021).Central and superficial brain lesions detected by MR imaging in HIV-1-infected patients with cryptococcal meningoencephalitis are in correlation with the host immunity and HAART therapy.

  9. Water intoxication in epileptic patients receiving carbamazepine.

    PubMed Central

    Perucca, E; Garratt, A; Hebdige, S; Richens, A

    1978-01-01

    Plasma sodium and osmolality were determined in 80 adult epileptic patients receiving chronic treatment with carbamazepine and in 50 control patients treated with other anticonvulsant drugs. Mean plasma osmolality was significantly lower in the carbamazepine-treated patients but mean plasma sodium did not differ in the two groups. Hyponatraemia was found in five of the carbamazine-treated patients and hypo-osmolality in six. None of the control patients had hyponatraemia and only one had a borderline low osmolality. Three of the 13 patients receiving carbamazepine alone were hyponatraemic. Plasma sodium concentration correlated negatively with both daily carbamazepine dose and serum carbamazepine level. Free water clearance after an oral water load was determined in six patients on carbamazepine alone and in six normal subjects not receiving drug therapy. The capacity of some of the patients to excrete the water load was found to be grossly impaired. PMID:681958

  10. Hyperimmune IV immunoglobulin treatment: a multicenter double-blind randomized controlled trial for patients with severe 2009 influenza A(H1N1) infection.

    PubMed

    Hung, Ivan F N; To, Kelvin K W; Lee, Cheuk-Kwong; Lee, Kar-Lung; Yan, Wing-Wa; Chan, Kenny; Chan, Wai-Ming; Ngai, Chun-Wai; Law, Kin-Ip; Chow, Fu-Loi; Liu, Raymond; Lai, Kang-Yiu; Lau, Candy C Y; Liu, Shao-Haei; Chan, Kwok-Hung; Lin, Che-Kit; Yuen, Kwok-Yung

    2013-08-01

    Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking. This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-IVIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-IVIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared. Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-IVIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04). Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality. ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov.

  11. Daclatasvir/asunaprevir/beclabuvir fixed-dose combination in Japanese patients with HCV genotype 1 infection.

    PubMed

    Toyota, Joji; Karino, Yoshiyasu; Suzuki, Fumitaka; Ikeda, Fusao; Ido, Akio; Tanaka, Katsuaki; Takaguchi, Koichi; Naganuma, Atsushi; Tomita, Eiichi; Chayama, Kazuaki; Fujiyama, Shigetoshi; Inada, Yukiko; Yoshiji, Hitoshi; Watanabe, Hideaki; Ishikawa, Hiroki; Hu, Wenhua; McPhee, Fiona; Linaberry, Misti; Yin, Philip D; Swenson, Eugene Scott; Kumada, Hiromitsu

    2017-03-01

    DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non-nucleoside NS5B inhibitor), has achieved high rates of sustained virologic response at post-treatment Week 12 (SVR12) in phase 3 studies. In this phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for 24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 % genotype 1b). SVR12 rates ≥95 % were achieved in both treatment-naive (N = 152) and interferon-experienced (N = 65) cohorts treated with DCV-TRIO for 12 weeks and were comparable across patient subgroups, including patients aged ≥65 years and those with cirrhosis. DUAL recipients (N = 75) had an SVR12 rate of 87 %. In the absence of baseline resistance-associated polymorphisms at positions NS5A-Y93H or -L31, SVR12 rates were 98 % with DCV-TRIO or DUAL. Among genotype 1b-infected patients with baseline Y93H or L31 polymorphisms, 35/38 (92 %) DCV-TRIO recipients, and 7/16 (44 %) DUAL recipients achieved SVR12. Adverse events, mostly liver related, led to treatment discontinuation in 10 % of DCV-TRIO recipients. In this group, SVR12 was achieved by 3/9 patients who discontinued before Week 4 and by 12/12 patients who completed ≥4 weeks of DCV-TRIO. Treatment-related serious adverse events occurred in 4 and 3 % of DCV-TRIO and DUAL recipients, respectively. Seven patients (9 %) discontinued DUAL due to adverse events. No deaths occurred. SVR12 was achieved by 96 % of Japanese patients with HCV genotype 1 infection after 12 weeks of treatment with the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.

  12. Fatigue in patients receiving palliative care.

    PubMed

    Ream, Emma

    This article discusses fatigue in patients receiving palliative care. The article initially considers the prevalence of fatigue in different groups of palliative care patients, then addresses how it manifests before reviewing how it can be assessed and managed. The focus of the article is on palliative care but it draws on, and has relevance for, chronic disease more widely.

  13. Barefoot Plantar Pressure Indicates Progressive Neurological Damage in Patients with Human T-Cell Lymphotropic Virus Type 1 Infection

    PubMed Central

    Vasconcelos, Beatriz Helena B.; Souza, Givago S.; Barroso, Tatiana G. C. P.; Silveira, Luiz Carlos L.; Sousa, Rita Catarina M.; Callegari, Bianca; Xavier, Marília B.

    2016-01-01

    Background The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals. Methodology We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient’s clinical history and examinations of the patient’s reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed. Main Findings The prevalence of neurological disturbances—altered reflexes and skin tactile sensitivity and increased risk of falling—was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV-1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects. Conclusions The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection. PMID:26998608

  14. BRAIN ABSCESS DUE TO Staphylococcus aureus OF CRYPTOGENIC SOURCE IN AN HIV-1 INFECTED PATIENT IN USE OF ANTIRETROVIRAL THERAPY

    PubMed Central

    de OLIVEIRA, Anna Paula Romero; PAPPALARDO, Mara Cristina; DANTAS, Daniel; LINS, Diogo; VIDAL, José Ernesto

    2016-01-01

    The spectrum of neurological complications associated with human immunodeficiency virus type 1 (HIV-1) infection is broad. The most frequent etiologies include primary diseases (caused by HIV itself) or secondary diseases (opportunistic infections or neoplasms). Despite these conditions, HIV-infected patients are susceptible to other infections observed in patients without HIV infection. Here we report a rare case of a brain abscess caused by Staphylococcus aureus in an HIV-infected patient. After drainage of the abscess and treatment with oxacilin, the patient had a favorable outcome. This case reinforces the importance of a timely neurosurgical procedure that supported adequate management of an unusual cause of expansive brain lesions in HIV-1 infected patients. PMID:27074328

  15. Safety of daptomycin in patients receiving hemodialysis.

    PubMed

    Mueller, Bruce A; Crompton, Jason A; Donovan, Brian J; Yankalev, Sara; Lamp, Kenneth C

    2011-07-01

    To determine the safety of daptomycin administered using a variety of doses and dosing frequencies in patients receiving intermittent hemodialysis who had probable or confirmed gram-positive infections. Analysis of data from the Cubicin Outcomes Registry and Experience (CORE), a multicenter, retrospective, observational registry. Fifty-four study sites, mostly (46%) large teaching hospitals. Three hundred ninety-three adults in the CORE registry who received intermittent hemodialysis between 2005 and 2008. The CORE registry is noninterventional and collects standard-of-care data on daptomycin treatment from health care institutions. Of the 393 patients, 370 (94%) could be categorized by daptomycin dosing frequency: every 48 hours (251 patients [64%]), 3 times/week (87 [22%]), and every 24 hours (32 [8%]); the remaining 23 (6%) had unreported dosing frequencies or received a single dose of daptomycin. Three hundred eighty-four patients (98%) received part of their daptomycin therapy as an inpatient and 129 patients (33%) received part of their daptomycin therapy in an intensive care setting. The primary infection type was bacteremia (224 patients [57%]), and the most common pathogen was Staphylococcus aureus (155 patients [39%]). Thirty-eight adverse events possibly related to daptomycin occurred in 28 patients (7%); increased blood creatine kinase level (7 patients [1.8%]) was the most common adverse event. Adverse-event rates were similar across all dosing regimens. In these patients undergoing hemodialysis, daptomycin was a well-tolerated treatment for gram-positive infections across several doses and dosing frequencies. Further study in prospective trials is warranted.

  16. Taste Alteration in Patients Receiving Chemotherapy

    PubMed Central

    Sözeri, Elif; Kutlutürkan, Sevinç

    2015-01-01

    Objective This study is aimed to determine factors that affect conditions of patients receiving chemotherapy in terms of experienced taste alteration. Materials and Methods In this descriptive study, 184 patients receiving chemotherapy were included in the sample. Data were collected during the period of December 2013 to May 2014 using “Patient Characteristics Identification Form” and “Chemotherapy-induced Taste Alteration Scale (CiTAS).” The data were analyzed using SPSS 20 (SPSS Inc., Chicago IL, USA) statistical software in terms of number, percentage, Mann-Whitney U test, and Kruskal-Wallis H test. Results The mean age of the patients was 55.5±11.8 and 57.1% of them were female. The clinical diagnosis of the patients were most frequently breast cancer (n=46), colorectal cancer (n=45), and lung cancer (n=25). Furthermore, 37.5% of the patients were in clinical stage II; 15.8% of the patients received paclitaxel+herceptin and 14.1% received gemcitabine+cisplatin chemotherapy protocols. Data demonstrated significant differences in mean scores (p<0.05) taken from “Decline in Basic Taste” and “Phantogeusia and Parageusia” subscales with patients with or without xerostomia. There were significant differences in the average scores of the subscales between those with and without a sore mouth “Discomfort” and “General taste alterations” (p<0.05). Conclusion It has been established that patients receiving chemotherapy experience substantial alteration in taste by exposure of different subscales of CiTAS. Analysis of scores collected from different subscales of CiTAS with respect to sociodemographic and pathological differences showed that patients with xerostomia and sore mouth experienced more severe taste alterations.

  17. The combination of MK-5172, peginterferon, and ribavirin is effective in treatment-naive patients with hepatitis C virus genotype 1 infection without cirrhosis.

    PubMed

    Manns, Michael P; Vierling, John M; Bacon, Bruce R; Bruno, Savino; Shibolet, Oren; Baruch, Yaacov; Marcellin, Patrick; Caro, Luzelena; Howe, Anita Y M; Fandozzi, Christine; Gress, Jacqueline; Gilbert, Christopher L; Shaw, Peter M; Cooreman, Michael P; Robertson, Michael N; Hwang, Peggy; Dutko, Frank J; Wahl, Janice; Mobashery, Niloufar

    2014-08-01

    MK-5172 is an inhibitor of the hepatitis C virus (HCV) nonstructural protein 3/4A protease; MK-5172 is taken once daily and has a higher potency and barrier to resistance than licensed protease inhibitors. We investigated the efficacy and tolerability of MK-5172 with peginterferon and ribavirin (PR) in treatment-naive patients with chronic HCV genotype 1 infection without cirrhosis. We performed a multicenter, double-blind, randomized, active-controlled, dose-ranging, response-guided therapy study. A total of 332 patients received MK-5172 (100, 200, 400, or 800 mg) once daily for 12 weeks in combination with PR. Patients in the MK-5172 groups received PR for an additional 12 or 36 weeks, based on response at week 4. Patients in the control group (n = 66) received a combination of boceprevir and PR, dosed in accordance with boceprevir's US product circular. At 24 weeks after the end of therapy, sustained virologic responses were achieved in 89%, 93%, 91%, and 86% of the patients in the groups given the combination of PR and MK-5172 (100, 200, 400, or 800 mg), respectively, vs 61% of controls. In the MK-5172 group receiving 100 mg, 91% of patients had undetectable levels of HCV RNA at week 4 and qualified for the short duration of therapy. The combination of MK-5172 and PR generally was well tolerated. Transient increases in transaminase levels were noted in the MK-5172 groups given 400 and 800 mg, at higher frequencies than in the MK-5172 groups given 100 or 200 mg, or control groups. Once-daily MK-5172 (100 mg) with PR for 24 or 48 weeks was highly effective and well tolerated among treatment-naive patients with HCV genotype 1 infection without cirrhosis. Studies are underway to evaluate interferon-free MK-5172-based regimens. ClinicalTrials.gov number: NCT01353911. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  18. Maraviroc for previously treated patients with R5 HIV-1 infection.

    PubMed

    Gulick, Roy M; Lalezari, Jacob; Goodrich, James; Clumeck, Nathan; DeJesus, Edwin; Horban, Andrzej; Nadler, Jeffrey; Clotet, Bonaventura; Karlsson, Anders; Wohlfeiler, Michael; Montana, John B; McHale, Mary; Sullivan, John; Ridgway, Caroline; Felstead, Steve; Dunne, Michael W; van der Ryst, Elna; Mayer, Howard

    2008-10-02

    CC chemokine receptor 5 antagonists are a new class of antiretroviral agents. We conducted two double-blind, placebo-controlled, phase 3 studies--Maraviroc versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) 1 and MOTIVATE 2--with patients who had R5 human immunodeficiency virus type 1 (HIV-1) only. They had been treated with or had resistance to three antiretroviral-drug classes and had HIV-1 RNA levels of more than 5000 copies per milliliter. The patients were randomly assigned to one of three antiretroviral regimens consisting of maraviroc once daily, maraviroc twice daily, or placebo, each of which included optimized background therapy (OBT) based on treatment history and drug-resistance testing. Safety and efficacy were assessed after 48 weeks. A total of 1049 patients received the randomly assigned study drug; the mean baseline HIV-1 RNA level was 72,400 copies per milliliter, and the median CD4 cell count was 169 per cubic millimeter. At 48 weeks, in both studies, the mean change in HIV-1 RNA from baseline was greater with maraviroc than with placebo: -1.66 and -1.82 log(10) copies per milliliter with the once-daily and twice-daily regimens, respectively, versus -0.80 with placebo in MOTIVATE 1, and -1.72 and -1.87 log(10) copies per milliliter, respectively, versus -0.76 with placebo in MOTIVATE 2. More patients receiving maraviroc once or twice daily had HIV-1 RNA levels of less than 50 copies per milliliter (42% and 47%, respectively, vs. 16% in the placebo group in MOTIVATE 1; 45% in both maraviroc groups vs. 18% in MOTIVATE 2; P<0.001 for both comparisons in each study). The change from baseline in CD4 counts was also greater with maraviroc once or twice daily than with placebo (increases of 113 and 122 per cubic millimeter, respectively, vs. 54 in MOTIVATE 1; increases of 122 and 128 per cubic millimeter, respectively, vs. 69 in MOTIVATE 2; P<0.001 for both comparisons in each study). Frequencies of adverse

  19. [Are domiciliary care patients receiving adequate thromboprophylaxis?].

    PubMed

    Cátedra, B; Muñoz, F; Cabello, L

    2014-01-01

    The study aims to determine the percentage of patients treated at home with an indication of prophylaxis of thromboembolic disease (TED) according to the PRETEMED guidelines and whether they receive such prophylaxis. A cross-sectional descriptive study was conducted in Segovia Palace Health Centre (Madrid). to be included in the domiciliary care protocol. terminal patient, hospitalised or surgery in the last 3 months. The variables used include, age, sex, duration of domiciliary care, mobility, anticoagulant or antiplatelet treatment and reason, and associated and precipitating factors to calculate the risk of TED according to the PRETEMED guidelines, and if they receive such prophylaxis, by reviewing computerised medical records and meeting with the staff responsible. The study included a total of 187 patients, of whom 81% were women There was a significant differences in mean age by sex (men, 76.91 years, 95% CI; 72.59-81.24, and women, 86.72 years, 95% CI; 72.59-81.24, P<.05). Almost two-thirds (65%) walked in the home. There were 3.7% patients who had an indication for receiving prophylaxis, but did not receive it, although 85.8% of them were on anticoagulants or antiplatelet therapy for other reasons. Most patients in domiciliary care have a low baseline risk of developing a TED episode in our study. There should be more emphasis placed on the prophylaxis of TED in acute medical episodes in which patients with slightly elevated risk may increase the likelihood of TED. Observational studies should be conducted to study the baseline risk and the subsequent development of TED in the population receiving home care. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  20. Perturbations of Monocyte Subsets and Their Association with T Helper Cell Differentiation in Acute and Chronic HIV-1-Infected Patients

    PubMed Central

    Chen, Peng; Su, Bin; Zhang, Tong; Zhu, Xiaojing; Xia, Wei; Fu, Yan; Zhao, Guoxian; Xia, Huan; Dai, Lili; Sun, Lijun; Liu, Lifeng; Wu, Hao

    2017-01-01

    Monocytes have been recently subdivided into three subsets: classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) subsets, but phenotypic and functional abnormalities of the three monocyte subsets in HIV-1 infection have not been fully characterized, especially in acute HIV-1 infection (AHI). In the study, we explored the dynamic changes of monocyte subsets and their surface markers, and the association between monocyte subsets and the IFN-γ, interleukin (IL)-4, IL-17, and TNF-α producing CD4+ T cells in acute and chronic HIV-1-infected patients. We found that, in the acute HIV-1-infected individuals, the frequency of the intermediate CD14++CD16+ monocyte subsets, the CD163 density and HLA-DR density on intermediate CD14++CD16+ monocytes, and plasma soluble form of CD163 (sCD163) were significantly higher than that in healthy controls. Intermediate CD14++CD16+ monocyte subsets and their HLA-DR expression levels were inversely correlated with the CD4+ T cell counts, and the intermediate CD14++CD16+ monocytes were positively correlated with plasma sCD163. In contrast to the non-classical CD14+CD16++ and classical CD14++CD16− monocyte subsets, the frequency of the intermediate CD14++CD16+ monocytes was positively associated with the frequency of IFN-γ and IL-4 producing CD4+ T cells in HIV-1-infected patients. Taken together, our observations provide new insight into the roles of the monocyte subsets in HIV pathogenesis, particularly during AHI, and our findings may be helpful for the treatment of HIV-related immune activation. PMID:28348563

  1. Outcomes in older versus younger patients over 96 weeks in HIV-1- infected patients treated with rilpivirine or efavirenz in ECHO and THRIVE.

    PubMed

    Ryan, Robert; Dayaram, Yaswant K; Schaible, Deborah; Coate, Bruce; Anderson, David

    2013-10-01

    Increasing life expectancy of HIV-1-infected patients raises interest in how trial results apply to older patients. This post-hoc analysis evaluated potential differences in efficacy and safety in older (≥50 years) versus younger (<50 years) patients in the ECHO and THRIVE trials over 96 weeks. HIV-infected, treatment-naïve adults were randomized to receive rilpivirine (RPV) or efavirenz (EFV), plus a background regimen. Virologic response rates (FDA snapshot analysis; HIV-1 RNA <50 copies/mL) were assessed at Week 96. Total-body bone mineral density was evaluated at baseline and Week 96 by dual-energy X-ray absorptiometry scans. Serum concentrations of 25-hydroxy vitamin D (ECHO trial only) were also measured at baseline, Week 24 and Week 48. 1368 patients were treated. At Week 96, virologic response rates were similar between older (77%) and younger (76%) RPV-treated patients and numerically higher in older (84%) versus younger (76%) EFV-treated patients. No clinically relevant age-related differences were observed in immunologic responses. Small differences were noted in older versus younger patients in adverse events (higher rates of depression, insomnia, and rash in older EFV-treated patients), laboratory abnormalities (increased low-density lipoprotein cholesterol and hyperglycemia in older EFV-treated patients and increased amylase in older patients across treatments), bone mineral density (larger decreases in older patients across treatments), and progression to severe vitamin D deficiency (greater in older versus younger EFV-treated patients). Efficacy and safety outcomes were generally similar in older versus younger patients in the ECHO and THRIVE trials.

  2. Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient.

    PubMed

    Balotta, C; Bagnarelli, P; Violin, M; Ridolfo, A L; Zhou, D; Berlusconi, A; Corvasce, S; Corbellino, M; Clementi, M; Clerici, M; Moroni, M; Galli, M

    1997-08-01

    Recent research has found that entry of non-syncytium-inducing (NSI), monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that delta 32/delta 32 homozygous individuals are protected against infection. To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects. CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation. The wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype. delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.

  3. Trans-Activation Response Element RNA is Detectable in the Plasma of a Subset of Aviremic HIV-1-Infected Patients.

    PubMed

    Hladnik, Anžej; Ferdin, Jana; Goričar, Katja; Deeks, G Steven; Peterlin, M Boris; Plemenitaš, Ana; Vita, Dolžan; Metka, Lenassi

    2017-09-01

    Determining the HIV-1 reservoir size in infected individuals is of great importance for improvement of their treatment. Plasma trans-activation response element (TAR) RNA has been suggested as one of the possible biomarkers. TAR RNA is produced during non-processive transcription in HIV-1 productively infected and latent T cells. Here, plasma samples and paired exosome samples of 55 subjects from the observational SCOPE cohort were analysed for the presence of TAR RNA. First, a PCR-based assay was optimized, which provided 100% specificity and 100% sensitivity in differentiating HIV-1 infected non-controllers from uninfected individuals. Next, TAR RNA was detected in the plasma of 63% of aviremic HIV-1-infected patients, who were either treated with antiretroviral therapy or were elite controllers. Although TAR RNA levels did not correlate with patient gender, age, CD4 levels, CD8 levels, they tended to correlate with CD4/CD8 ratio (P = 0.047). This study is the first to investigate plasma TAR RNA in a relatively large cohort of HIV-1-infected patients. We additionally show that the TAR RNA molecules in the plasma of aviremic patients are not limited to exosomes.

  4. Hypersensitivity reactions in patients receiving hemodialysis.

    PubMed

    Butani, Lavjay; Calogiuri, Gianfranco

    2017-06-01

    To describe hypersensitivity reactions in patients receiving maintenance hemodialysis. PubMed search of articles published during the past 30 years with an emphasis on publications in the past decade. Case reports and review articles describing hypersensitivity reactions in the context of hemodialysis. Pharmacologic agents are the most common identifiable cause of hypersensitivity reactions in patients receiving hemodialysis. These include iron, erythropoietin, and heparin, which can cause anaphylactic or pseudoallergic reactions, and topical antibiotics and anesthetics, which lead to delayed-type hypersensitivity reactions. Many hypersensitivity reactions are triggered by complement activation and increased bradykinin resulting from contact system activation, especially in the context of angiotensin-converting enzyme inhibitor use. Several alternative pharmacologic preparations and dialyzer membranes are available, such that once an etiology for the reaction is established, recurrences can be prevented without affecting the quality of care provided to patients. Although hypersensitivity reactions are uncommon in patients receiving hemodialysis, they can be life-threatening. Moreover, considering the large prevalence of the end-stage renal disease population, the implications of such reactions are enormous. Most reactions are pseudoallergic and not mediated by immunoglobulin E. The multiplicity of potential exposures and the complexity of the environment to which patients on dialysis are exposed make it challenging to identify the precise cause of these reactions. Great diligence is needed to investigate hypersensitivity reactions to avoid recurrence in this high-risk population. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Color Preferences of Patients Receiving Elastic Ligatures

    PubMed Central

    Elekdag-Turk, Selma; Ozkalayci, Nurhat; Isci, Devrim; Turk, Tamer

    2010-01-01

    Objectives: To determine the color preferences for elastic ligatures among patients receiving fixed-appliance orthodontic therapy. Methods: Five hundred patients with metal brackets (336 female patients and 164 male patients) were included, and their color preferences for elastic ligatures were recorded using a color scale. Chi-square analysis was performed to evaluate the color preferences and to determine the influence of age and gender on color preferences (P<.05). Results: Two hundred and seventy-six patients (55.2%) preferred strikingly colorful elastic ligatures, while 224 patients (44.8%) preferred less noticeable elastic ligatures. No significant difference was observed between the color preferences of female and male patients (P>.05). However, significant differences were observed between the color preferences of adolescents and older patients (P<.001). Conclusions: Female patients preferred red–purple-colored tones, while male patients preferred blue–black-colored tones. Adolescents preferred colorful elastic ligatures, while older patients preferred ligatures with less-noticeable colors. A stock of 10–12 colorful and less-noticeable elastic ligatures seems to be adequate to ensure patient satisfaction. PMID:20396449

  6. Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure

    PubMed Central

    Kimulwo, Maureen J.; Okendo, Javan; Aman, Rashid A.; Ogutu, Bernhards R.; Kokwaro, Gilbert O.; Ochieng, Dorothy J.; Muigai, Anne W. T.; Oloo, Florence A.

    2017-01-01

    Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therapy (ART). Blood plasma was collected at 1, 4 and 24 hours post-ART dosing from 58 subjects receiving NVP-containing ART and used to determine cNVP and viral load (VL). Median duration of treatment was 42 (range, 12–156) months, and 25 (43.1%) of the patients had virologic failure (VF). cNVP was significantly lower for VF than non- VF at 1hr (mean, 2,111ng/ml vs. 3,432ng/ml, p = 0.003) and at 4hr (mean 1,625ng/ml vs. 3,999ng/ml, p = 0.001) but not at 24hr post-ART dosing. Up to 53.4%, 24.1% and 22.4% of the subjects had good, fair and poor adherence respectively. cNVP levels peaked and were > = 3μg.ml at 4 hours in a majority of patients with good adherence and those without VF. Using a threshold of 3μg/ml for optimal therapeutic nevirapine level, 74% (43/58), 65.5% (38/58) and 86% (50/58) of all patients had sub-therapeutic cNVP at 1, 4 and 24 hours respectively. cNVP at 4 hours was associated with adherence (p = 0.05) and virologic VF (p = 0.002) in a chi-square test. These mean cNVP levels differed significantly in non-parametric tests between adherence categories at 1hr (p = 0.005) and 4hrs (p = 0.01) and between ART regimen categories at 1hr (p = 0.004) and 4hrs (p<0.0001). Moreover, cNVP levels correlated inversely with VL (p< = 0.006) and positively with adherence behavior. In multivariate tests, increased early peak NVP (cNVP4) was independently predictive of lower VL (p = 0.002), while delayed high NVP peak (cNVP24) was consistent with increased VL (p = 0.033). These data strongly assert the need to integrate plasma concentrations of NVP and that of other ART drugs into routine ART management of HIV-1 patients. PMID:28235021

  7. Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure.

    PubMed

    Kimulwo, Maureen J; Okendo, Javan; Aman, Rashid A; Ogutu, Bernhards R; Kokwaro, Gilbert O; Ochieng, Dorothy J; Muigai, Anne W T; Oloo, Florence A; Ochieng, Washingtone

    2017-01-01

    Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therapy (ART). Blood plasma was collected at 1, 4 and 24 hours post-ART dosing from 58 subjects receiving NVP-containing ART and used to determine cNVP and viral load (VL). Median duration of treatment was 42 (range, 12-156) months, and 25 (43.1%) of the patients had virologic failure (VF). cNVP was significantly lower for VF than non- VF at 1hr (mean, 2,111ng/ml vs. 3,432ng/ml, p = 0.003) and at 4hr (mean 1,625ng/ml vs. 3,999ng/ml, p = 0.001) but not at 24hr post-ART dosing. Up to 53.4%, 24.1% and 22.4% of the subjects had good, fair and poor adherence respectively. cNVP levels peaked and were > = 3μg.ml at 4 hours in a majority of patients with good adherence and those without VF. Using a threshold of 3μg/ml for optimal therapeutic nevirapine level, 74% (43/58), 65.5% (38/58) and 86% (50/58) of all patients had sub-therapeutic cNVP at 1, 4 and 24 hours respectively. cNVP at 4 hours was associated with adherence (p = 0.05) and virologic VF (p = 0.002) in a chi-square test. These mean cNVP levels differed significantly in non-parametric tests between adherence categories at 1hr (p = 0.005) and 4hrs (p = 0.01) and between ART regimen categories at 1hr (p = 0.004) and 4hrs (p<0.0001). Moreover, cNVP levels correlated inversely with VL (p< = 0.006) and positively with adherence behavior. In multivariate tests, increased early peak NVP (cNVP4) was independently predictive of lower VL (p = 0.002), while delayed high NVP peak (cNVP24) was consistent with increased VL (p = 0.033). These data strongly assert the need to integrate plasma concentrations of NVP and that of other ART drugs into routine ART management of HIV-1 patients.

  8. Awareness and education of patients receiving bisphosphonates.

    PubMed

    Bauer, Julia S; Beck, Nina; Kiefer, Julia; Stockmann, Philipp; Wichmann, Manfred; Eitner, Stephan

    2012-04-01

    Bisphosphonates are used to fight osteoporosis and for treating malignancies. In 2003, the first case reports appeared that described bisphosphonate-induced osteonecrosis of the jaw (BONJ). The aim of this study was to assess patient awareness of the adverse effects of bisphosphonates in order to improve cooperation among doctors and between doctors and patients. Patients with symptoms of osteoporosis, prostate cancer, or breast cancer were surveyed to determine their knowledge of bisphosphonates. The questionnaire comprised 12 questions that covered sociographic data, kind of medication, level of information, and side effects experienced. Out of 142 patients contacted, 55 participated in the study. 62% of patients received most of their knowledge about the prescribed drug from the package insert. Despite knowledge that the patient was under treatment with bisphosphonates, 80% of dental treatments were continued without modifications. Only 32% of patients that received intravenous bisphosphonate treatment were aware of the possible risks of developing BONJ. The level of information is poor concerning the side effects of bisphosphonates, particularly the risk of BONJ. Clinicians should aim to sensitize the relevant people about the risks before treatment. Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  9. Modulation of glutathione intracellular levels alters the spontaneous proliferation of lymphocyte from HTLV-1 infected patients.

    PubMed

    Novaes, Renata; Freire-de-Lima, Célio G; de Albuquerque, Raquel Cavalcanti; Affonso-Mitidieri, Ottilia R; Espindola, Otávio; Lima, Marco Antonio; de Andrada Serpa, Maria José; Echevarria-Lima, Juliana

    2013-09-01

    The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with neoplasias and inflammatory diseases, such as adult T-cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1-infected individuals present a spontaneous T lymphocyte proliferation. This phenomenon is related to the HTLV-1-proviral load and the persistence of the infection. Viral proteins induce many cellular mediators, which can be associated with the abnormal cellular proliferation. The intracellular levels of glutathione (GSH) are important to modulate the cellular proliferation. The aim of this study was to investigate the correlation between the modulation of intracellular GSH levels and the spontaneous lymphocyte proliferation during the HTLV-1 infection. Intracellular GSH level can be modulated by using dl-buthionine-[S,R]-sulfoximine (BSO, GSH synthesis inhibitor) and N-acetylcysteine (NAC, peptide precursor). Our results demonstrated that BSO was capable of inducing a decrease in the spontaneous proliferation of PBMC derived from HTLV-1 carriers. On the other hand, the GSH precursor induces an increase in mitogen-stimulated cellular proliferation in infected and uninfected individuals. Similar results were observed by the inhibition of ABCC1/MRP1 protein, augmenting the mitogen-induced proliferation. This effect can be related with an increase in the GSH levels since ABCC1/MRP1 transports GSH to the extracellular medium. There was a significant difference on the expression of CD69 and CD25 molecules during the lymphocyte activation. We did not observe any alterations on CD25 expression induced by BSO or NAC. However, our results demonstrated that NAC treatment induced an increase in CD69 expression on unstimulated CD8(+) T lymphocytes obtained from HTLV-1 infected individuals, healthy donors and HTLV carriers. Therefore, our results suggest that the cellular proliferation promoted by the infection with HTLV-1 and the activation

  10. Detection of the long noncoding RNAs nuclear-enriched autosomal transcript 1 (NEAT1) and metastasis associated lung adenocarcinoma transcript 1 in the peripheral blood of HIV-1-infected patients.

    PubMed

    Jin, C; Peng, X; Xie, T; Lu, X; Liu, F; Wu, H; Yang, Z; Wang, J; Cheng, L; Wu, N

    2016-01-01

    Long noncoding RNAs (lncRNAs) in HIV-1 infection have not been extensively studied. Here we detected two lncRNAs, nuclear-enriched autosomal transcript 1 (NEAT1) and metastasis associated lung adenocarcinoma transcript 1 (MALAT1), in peripheral blood mononuclear cells (PBMCs) and plasma of HIV-1-infected patients. Fifty-nine HIV-1-infected patients and 21 healthy controls were recruited for the study, of whom 31 patients were highly active antiretroviral therapy (HAART)-naïve and 28 patients had been receiving HAART for more than 1 year with undetectable viral loads. Total RNA was extracted from PBMCs and plasma, and levels of NEAT1 and MALAT1 were determined by quantitative real-time polymerase chain reaction. We found that the levels of NEAT1 and MALAT1 in PBMCs were up-regulated in HAART-naïve patients and were reduced in patients receiving HAART. NEAT1 was down-regulated in the plasma of infected patients and expression was correlated with CD4 T-cell count. Our findings suggest that NEAT1 and MALAT1 may interact with HIV-1 in vivo and that the presence of NEAT1 in plasma is a potential biomarker of HIV-1 infection. © 2015 British HIV Association.

  11. Interaction between artemether-lumefantrine and nevirapine-based antiretroviral therapy in HIV-1-infected patients.

    PubMed

    Kredo, T; Mauff, K; Van der Walt, J S; Wiesner, L; Maartens, G; Cohen, K; Smith, P; Barnes, K I

    2011-12-01

    Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the most commonly recommended first-line treatments for malaria and HIV, respectively, in Africa. Artemether, lumefantrine, and nevirapine are metabolized by the cytochrome P450 3A4 enzyme system, which nevirapine induces, creating potential for important drug interactions. In a parallel-design pharmacokinetic study, concentration-time profiles were obtained in two groups of HIV-infected patients: ART-naïve patients and those stable on nevirapine-based therapy. Both groups received the recommended artemether-lumefantrine dose. Patients were admitted for intense pharmacokinetic sampling (0 to 72 h) with outpatient sampling until 21 days. Concentrations of lumefantrine, artemether, dihydroartemisinin, and nevirapine were determined by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. The primary outcome was observed day 7 lumefantrine concentrations, as these are associated with therapeutic response in malaria. We enrolled 36 patients (32 females). Median (range) day 7 lumefantrine concentrations were 622 ng/ml (185 to 2,040 ng/ml) and 336 ng/ml (29 to 934 ng/ml) in the nevirapine and ART-naïve groups, respectively (P = 0.0002). The median artemether area under the plasma concentration-time curve from 0 to 8 h [AUC((0-8 h))] (P < 0.0001) and dihydroartemisinin AUC((60-68 h)) (P = 0.01) were lower in the nevirapine group. Combined artemether and dihydroartemisinin exposure decreased over time only in the nevirapine group (geometric mean ratio [GMR], 0.76 [95% confidence interval {CI}, 0.65 to 0.90]; P < 0.0001) and increased with the weight-adjusted artemether dose (GMR, 2.12 [95% CI, 1.31 to 3.45]; P = 0.002). Adverse events were similar between groups, with no difference in electrocardiographic Fridericia corrected QT and P-R intervals at the expected time of maximum lumefantrine concentration (T(max)). Nevirapine-based ART decreased artemether and

  12. Cumulative exposure to ritonavir-boosted atazanavir is associated with cholelithiasis in patients with HIV-1 infection.

    PubMed

    Nishijima, Takeshi; Shimbo, Takuro; Komatsu, Hirokazu; Hamada, Yohei; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Oka, Shinichi

    2014-05-01

    This study aimed to examine the effect of long-term treatment with ritonavir-boosted atazanavir (atazanavir/ritonavir) on cholelithiasis. A single-centre, cross-sectional study was conducted to elucidate the prevalence of cholelithiasis in patients with HIV-1 infection who underwent abdominal ultrasonography between January 2004 and March 2013. Univariate and multivariate logistic regression analyses were applied to estimate the effects of >2 years of atazanavir/ritonavir exposure on cholelithiasis as the primary exposure. Of the 890 study patients, 84 (9.4%) had >2 years of atazanavir/ritonavir exposure. Cholelithiasis was twice as frequent in those treated for >2 years with atazanavir/ritonavir [15 (18%) of 84 patients] compared with those treated for <2 years [72 (8.9%) of 806 patients] (P = 0.018). Univariate analysis showed a significant association between >2 years of atazanavir/ritonavir exposure and cholelithiasis (OR = 2.216; 95% CI = 1.206-4.073; P = 0.010) and the association almost persisted in multivariate analysis (adjusted OR = 1.806; 95% CI = 0.922-3.537; P = 0.085). Long-term treatment (>2 years) with other commonly used protease inhibitors, such as ritonavir-boosted lopinavir and ritonavir-boosted darunavir, was not associated with cholelithiasis in univariate and multivariate analysis. Additional analysis showed that >1 year of exposure to atazanavir/ritonavir was significantly associated with cholelithiasis (OR = 1.857; 95% CI = 1.073-3.214; P = 0.027), whereas >1 year of exposure to ritonavir-boosted lopinavir and ritonavir-boosted darunavir was not. Long-term treatment of patients with HIV-1 infection for >2 years with atazanavir/ritonavir was associated with an increased risk of cholelithiasis compared with patients with shorter exposure. Long-term exposure to atazanavir/ritonavir appears to increase the risk of cholelithiasis in patients with HIV-1 infection.

  13. Listeriosis in patients receiving biologic therapies.

    PubMed

    Bodro, M; Paterson, D L

    2013-09-01

    The evolution of inflammatory diseases has radically changed since the introduction of biologic therapies, such as tumour necrosis factor alpha inhibitors (anti-TNFα). They, therefore, represent a widely used therapeutic modality. Nevertheless, post-marketing studies reveal an increased risk of infection in patients taking these drugs, especially granulomatous infections such as listeriosis. We aimed to evaluate the reported cases of listeriosis in patients treated with biologic treatments. We used the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) from 2004 to 2011. We also perform a literature review of previously reported cases of listeriosis in patients taking biologic therapies. We identified 266 cases of Listeria monocytogenes infection associated with biologic therapies. The majority of patients were receiving infliximab (77.1 %), followed by etanercept (11.7 %), adalimumab (9.8 %), rituximab (4.1 %), abatacept (0.4 %) and golimumab (0.4 %). Indications for the use of biologics were as follows: 47.7 % for rheumatologic diseases, 38 % for inflammatory bowel diseases, 3.4 % for haematological diseases and 10.5 % for other indications. Seventy-three percent of the patients were receiving concomitant immunosuppressant drugs, especially steroids (56 %) and methotrexate (31.6 %). The median time to the onset of infection was 184 days. Mortality rates range from 11.1 % in adalimumab-treated patients to 27.3 % in rituximab-treated patients (p = 0.7). Listeriosis is common in biologics-treated patients, especially related to infliximab use given concomitantly with other immunosuppressive therapies. Infections after treatment with biologics mostly occurred in the first year after initiating treatment.

  14. Meta-analysis of diagnostic procedures for Pneumocystis carinii pneumonia in HIV-1-infected patients.

    PubMed

    Cruciani, M; Marcati, P; Malena, M; Bosco, O; Serpelloni, G; Mengoli, C

    2002-10-01

    Sputum induction is a simple and noninvasive procedure for Pneumocystis carinii pneumonia (PCP) diagnosis in human immunodeficiency virus-1-positive patients, although less sensitive than bronchoalveolar lavage (BAL). In order to obtain an overview of the diagnostic accuracy of sputum induction, a systematic review and meta-analysis of studies reporting the comparative sensitivity and specificity of BAL (the "gold standard") and sputum induction was performed. The odds ratio and related 95% confidence interval were calculated using summary receiving operating characteristic curves as well as fixed-effect and random-effect models. Based on pooled data, the negative and positive predictive values were calculated for a range of PCP prevalence using a Bayesian approach. Seven prospective studies assessed the comparative accuracy of BAL and sputum induction. On the whole, sputum induction demonstrated 55.5% sensitivity and 98.6% specificity. The sensitivity of sputum induction was significantly higher with immunofluorescence than with cytochemical staining (67.1 versus 43.1%). In settings of 25-60% prevalence of PCP, the positive and negative predictive values ranged 86-96.7 and 66.2-89.8, respectively, with immunofluorescence, and 79-94.4 and 53-83.5% with cytochemical staining. In conclusion, in a setting of low prevalence of Pneumocystis carinii pneumonia, sputum induction, particularly with immunostaining, appears to be adequate for clinical decision-making.

  15. Acne vulgaris and acne rosacea as part of immune reconstitution disease in HIV-1 infected patients starting antiretroviral therapy.

    PubMed

    Scott, Christopher; Staughton, Richard C D; Bunker, Christopher J; Asboe, David

    2008-07-01

    Immune reconstitution disease (IRD) has been widely reported following the commencement of antiretrovirals. We report a case series from a cohort of HIV-1-infected patients of whom four developed acne vulgaris and one developed acne rosacea after the initiation of antiretroviral therapy. Acne vulgaris, as part of IRD, has been reported only once in the literature, whereas acne rosacea has not, to our knowledge, previously been described. This serves as a reminder not to overlook dermatological manifestations of disease in patients with HIV infection after starting antiretrovirals.

  16. Acute hepatitis C in patients receiving hemodialysis.

    PubMed

    Griveas, I; Germanidis, G; Visvardis, G; Morice, Y; Perelson, A S; Pawlotsky, J M; Papadopoulou, D

    2007-01-01

    Hepatitis C virus (HCV) infection is frequent in patients with end-stage renal disease treated by chronic dialysis, with a prevalence varying from 10-65% according to the geographical data. The prevalence is significantly associated with the duration of dialysis and the number of transfused blood products[1,2] and has dramatically declined with efficient blood screening.[3] We studied patients with acute HCV infection in a dialysis unit. The diagnosis was based on both anti-HCV detection and HCV-RNA detection. Other virological tools including HCV genotype determination was also used to tailor treatment to the individual patient and determine its efficacy for a one-year follow-up period. Seventeen patients (7 male and 10 female, mean age: 63.7 +/- 11.6 SD) with acute hepatitis C were enrolled to our study. All of them were followed up for a period of one year after the diagnosis was established. Phylogenetic analysis distinguished two separate HCV subtypes 1b, which were both responsible for this acute infection (see Figure 1). These types did not differ in their behavior on the clinical situation of our patients, as confirmed by the fact that in both groups of patients, there was only one patient who presented with acute illness. Six patients of our study group, three months after the acute infection, received pegylated interferon (Peg-IFNa2a) 135 mug for a six-month period. Four of them responded very well to therapy and at the first determination HCV RNA was below the cutoff point. One of our patients with very high HCV levels (HCV RNA > 50,000,000 IU/mL), despite receiving the same therapy, did not respond well and developed cirrhosis. In conclusion, it is clear from our experience that better information is needed about the current incidence, prevalence, and risk factors for HCV infection in dialysis patients. Algorithms for the diagnosis and management of hepatitis C should be developed by academic societies. Routine screening for hepatitis C also would allow

  17. Tolerability and activity of a new recombinant interferon-alpha B/D hybrid in patients with HIV-1 infection.

    PubMed

    Frissen, P H; Brinkman, K; Ten Napel, C H; van der Ende, I M; van Buuren, I A; Boucher, C A; Reiss, P; Lange, J M

    1996-04-01

    The maximum tolerated dose (MTD) and toxicity profile of a new recombinant interferon-alpha B/D hybrid (IFN-alpha B/D) in HlV-1-infected patients were determined in an outpatient, dose-escalating study with dose groups of three patients: 16, 32, 48, 64, 96 and 112 million international units (MIU) three times weekly subcutaneously during 12 weeks. The MTD was the last dose level just below the dose level at which more than one patient experienced > or = grade 3 toxicity. The study also searched for preliminary evidence of efficacy of IFN-alpha B/D. Sixteen HIV-1-infected patients with CD4 cell counts > or = 200/mm3 were enrolled: eight were asymptomatic and eight had symptomatic disease. Two patients were excluded as a result of protocol violations. Five patients (36 per cent; one at each tested dose level) discontinued prematurely due to side effects. One patient was lost to follow-up. Twelve patients (87 per cent) experienced > or = grade 2 toxicity. Toxicity > or = grade 3 occurred in none of three patients assigned to 16 MIU, one of five assigned to 32 MIU (fatigue), one of three assigned to 48 MIU (haemorrhagic colitis) and two of three assigned to 64 MIU (fatigue). One patient (48 MIU) had reversible cardiomegaly. Progressive weight loss was experienced by 12 of 14 participants. Serum HIV-1 p24 antigen declined in nine of 11 antigenaemic patients (seven persistently > 50 per cent) without a clear dose-response relationship. CD4 percentages showed no consistent pattern and T cell reactivity diminished. The tolerability and toxicity profile of IFN-alpha B/D appear to be fairly similar to that of other types of IFN-alpha.

  18. Intensification of Antiretroviral Therapy with a CCR5 Antagonist in Patients with Chronic HIV-1 Infection: Effect on T Cells Latently Infected

    PubMed Central

    Vallejo, Alejandro; Hernández-Novoa, Beatriz; Abad, María; Madrid, Nadia; Dahl, Viktor; Rubio, Rafael; Moreno, Ana M.; Dronda, Fernando; Casado, José Luis; Navas, Enrique; Pérez-Elías, María Jesús; Zamora, Javier; Palmer, Sarah; Muñoz, Eduardo; Muñoz-Fernández, María Ángeles; Moreno, Santiago

    2011-01-01

    Objective The primary objective was to assess the effect of MVC intensification on latently infected CD4+ T cells in chronically HIV-1-infected patients receiving antiretroviral therapy. Methods We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation. Results Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4+ or CD8+ counts, although a significant decrease was found in the proportion of HLA-DR+/CD38+ CD4+ and CD8+ T-cells. LPS and sCD14 levels increased. Conclusions Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results. Trial Registration ClinicalTrials.gov NCT00795444 PMID:22174752

  19. Pneumatosis Intestinalis in Patients Receiving Tube Feeds.

    PubMed

    Cavalea, Alexander C; Heidel, Robert E; Daley, Brian J; Lawson, Christy M; Benton, Darrell A; McLoughlin, James M

    2017-08-01

    Pneumatosis intestinalis (PI) identified on computed tomography (CT) suggests an underlying pathology including bowel ischemia. Patients receiving tube feeds can develop PI, potentially requiring surgical intervention. We identify clinical factors in PI to predict those that may be safe to observe versus those that need immediate intervention. We retrospectively reviewed patients from a single institution from 2008 to 2016 with CT findings of PI and an enteric feeding tube. Patients who had not received tube feeds within one week of the CT were excluded. We analyzed clinical, operative, and outcome data to differentiate benign from pathologic outcomes. P values < 0.05 were set as significant. Forty patients were identified. We classified 24 as benign (no intervention) and 16 as pathologic (requiring intervention). A pathologic outcome was demonstrated for free fluid on CT [odds ratio (OR) = 5.00, confidence interval (CI) 1.23-20.30, P = 0.03)], blood urea nitrogen (BUN) elevation (OR = 8.27, CI 1.53-44.62, P = 0.01), creatinine (Cr) elevation (OR = 5.00, CI 1.27-19.62, P = 0.02), BUN/Cr ratio >30 (OR = 8.57, CI 1.79-40.98, P = 0.006), and vomiting/feeding intolerance (OR = 9.38, CI 1.64-53.62, P = 0.01). Bowel function within 24 hours of the CT, bowel dilatation (small ≥ 3 cm; large ≥6 cm), and lactic acidemia were not significant. Peritonitis was only seen in pathologic states, but this did not reach statistical significance (P = 0.06). This represents the largest single-center retrospective analysis of tube feeding-induced PI to date. The presence of free fluid on CT, BUN and Cr elevation, BUN/Cr >30, vomiting/feeding intolerance and peritonitis were predictive of a pathologic etiology of PI.

  20. Psychiatric Symptoms in Patients Receiving Dolutegravir

    PubMed Central

    Fettiplace, Anna; Stainsby, Chris; Winston, Alan; Givens, Naomi; Puccini, Sarah; Vannappagari, Vani; Hsu, Ricky; Fusco, Jennifer; Quercia, Romina; Aboud, Michael

    2017-01-01

    Introduction: Psychiatric symptoms (PSs) are reported to occur frequently in people living with HIV and may be associated with specific antiretrovirals. We analyzed PSs observed with dolutegravir (DTG) and other frequently prescribed anchor drugs. Methods: Selected PSs (insomnia, anxiety, depression, and suicidality) occurring in HIV-positive patients during DTG treatment across 5 randomized clinical trials (3 double-blind), in the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, and among cases spontaneously reported to ViiV Healthcare were analyzed. Results: In clinical trials, PSs were reported at low and similar rates in patients receiving DTG or comparators [atazanavir, darunavir, efavirenz, or raltegravir (RAL)]. Insomnia was most commonly reported. The highest rates were observed in SINGLE (DTG 17%, efavirenz 12%), with consistently lower rates in the other trials (DTG: 3%–8% versus comparator: 3%–7%). More efavirenz-treated patients withdrew because of PSs than patients treated with other anchor drugs. In OPERA, history of PSs at baseline was lowest in efavirenz-treated patients compared with patients treated with DTG, RAL, or darunavir. Despite baseline differences, prevalence and incidence during treatment were similar across the 4 anchor drugs. Withdrawal rates for PSs were lowest for DTG (0%–0.6%) and highest for RAL (0%–2.5%). Spontaneously reported events were similar in nature to clinical trial data. Conclusions: Analysis of 3 different data sources shows that, similar to other frequently prescribed anchor drugs to treat HIV infection, PSs are also reported in DTG-treated patients. These events are reported with low frequency and rarely necessitate DTG discontinuation. PMID:27984559

  1. Psychiatric Symptoms in Patients Receiving Dolutegravir.

    PubMed

    Fettiplace, Anna; Stainsby, Chris; Winston, Alan; Givens, Naomi; Puccini, Sarah; Vannappagari, Vani; Hsu, Ricky; Fusco, Jennifer; Quercia, Romina; Aboud, Michael; Curtis, Lloyd

    2017-04-01

    Psychiatric symptoms (PSs) are reported to occur frequently in people living with HIV and may be associated with specific antiretrovirals. We analyzed PSs observed with dolutegravir (DTG) and other frequently prescribed anchor drugs. Selected PSs (insomnia, anxiety, depression, and suicidality) occurring in HIV-positive patients during DTG treatment across 5 randomized clinical trials (3 double-blind), in the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, and among cases spontaneously reported to ViiV Healthcare were analyzed. In clinical trials, PSs were reported at low and similar rates in patients receiving DTG or comparators [atazanavir, darunavir, efavirenz, or raltegravir (RAL)]. Insomnia was most commonly reported. The highest rates were observed in SINGLE (DTG 17%, efavirenz 12%), with consistently lower rates in the other trials (DTG: 3%-8% versus comparator: 3%-7%). More efavirenz-treated patients withdrew because of PSs than patients treated with other anchor drugs. In OPERA, history of PSs at baseline was lowest in efavirenz-treated patients compared with patients treated with DTG, RAL, or darunavir. Despite baseline differences, prevalence and incidence during treatment were similar across the 4 anchor drugs. Withdrawal rates for PSs were lowest for DTG (0%-0.6%) and highest for RAL (0%-2.5%). Spontaneously reported events were similar in nature to clinical trial data. Analysis of 3 different data sources shows that, similar to other frequently prescribed anchor drugs to treat HIV infection, PSs are also reported in DTG-treated patients. These events are reported with low frequency and rarely necessitate DTG discontinuation.

  2. Effectiveness of enfuvirtide in a cohort of highly antiretroviral-experienced HIV-1-infected patients in Mexico.

    PubMed

    Huerta-García, Gloria; Chavez-García, Marcelino; Mata-Marín, José Antonio; Sandoval-Ramírez, Jorge; Domínguez-Hermosillo, Juan; Rincón-Rodríguez, Ana Lourdes; Gaytán-Martínez, Jesús

    2014-01-01

    Treatments in patients with multidrug resistance often involve the use of multiple agents with partial antiviral activity and overlapping metabolic toxicities. Enfuvirtide is therefore a welcome addition to the antiretroviral management of patients with multiclass resistant virus, given the low risk of systemic toxicities and novel mechanism of action relative to existing drug classes. The aim of this study was to evaluate the effectiveness of ENF plus optimized background regimen (OBR) in a Mexican cohort of highly HIV-1 ARV-experienced patients. Prospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ENF-containing regimen. The effectiveness of ENF treatment was evaluated with percentages of undetectable HIV-1 RNA viral load after 24 and 48 weeks of treatment, and changes in CD4+ cell counts. Forty patients >18 years were included. After 24 weeks of treatment, 91% of patients had HIV-1 RNA viral load <400 copies/mL and 65.8% had <50 copies/mL. At week 48 of treatment, 81.4% of the patients had HIV-1 RNA <400 copies/mL and 55.5% had <50 copies/mL; in both cases p <0.0001 compared to baseline. Increase CD4+ cells were also statistically significant at weeks 24 and 48 with respect to the baseline. Pain at the site of injection was the main adverse event in 100% of patients. Our study provides clinically important evidence of the effectiveness and safety of ENF in highly ARV-experienced HIV-1-infected patients. These findings strengthen the results of previous randomized controlled trials with this agent.

  3. Off-label use of rilpivirine in combination with emtricitabine and tenofovir in HIV-1-infected pediatric patients

    PubMed Central

    Falcon-Neyra, Lola; Palladino, Claudia; Navarro Gómez, María Luisa; Soler-Palacín, Pere; González-Tomé, María Isabel; De Ory, Santiago J.; Frick, Marie Antoinette; Fortuny, Clàudia; Noguera-Julian, Antoni; Moreno, Elena Bermúdez; Santos, Juan Luis; Olbrich, Peter; López-Cortés, Luis F.; Briz, Verónica; Neth, Olaf

    2016-01-01

    Abstract To assess the safety and efficacy of rilpivirine in combination with emtricitabine and tenofovir (RPV/FTC/TDF) as a once-daily single-tablet regimen (STR) in HIV-1-infected children and adolescents we performed a multicenter case series study of HIV-1-infected patients. Inclusion criteria were initiation of therapy with RPV/FTC/TDF before the age of 18. Patients were divided into undetectable viral load (uVL) group, HIV-1 RNA < 20 copies/mL on stable combined antiretroviral therapy (cART), and detectable viral load (dVL) group, HIV-1 RNA ≥ 20 copies/mL at RPV/FTC/TDF initiation. Patients were monitored from the date of RPV/FTC/TDF initiation until June 30, 2015, RPV/FTC/TDF discontinuation or failure to follow-up. Seventeen patients (8 in uVL and 9 in dVL group) with age between 11.6 and 17.6 were included. Reasons for switching were toxicity (n = 4) and simplification (n = 4) in uVL; viral failure (n = 8) and cART initiation (n = 1) in the dVL group. After a median follow-up of 90 (uVL) and 40 weeks (dVL), 7/8 (86%) patients maintained and 8/9 (89%) achieved and maintained HIV-1 suppression. Median CD4 count increased from 542 to 780/μL (uVL, P = 0.069) and 480 to 830/μL (dVL, P = 0.051). Five patients (2 in uVL and 3 in dVL) improved their immunological status from moderate to no immunosuppression. Serum lipid profiles improved in both groups; cholesterol dropped significantly in the dVL group (P = 0.008). Grade 1 laboratory adverse events (AEs) were observed in 3 patients. No clinical AEs occurred. Adherence was complete in 9 patients (5 in uVL and 4 in dVL); 1 adolescent interrupted treatment. Once-daily STR with RPV/FTC/TDF may be a safe and effective choice in selected HIV-1-infected adolescents and children. PMID:27310962

  4. Paradoxical responses in a cohort of HIV-1-infected patients with mycobacterial disease.

    PubMed

    Olalla, J; Pulido, F; Rubio, R; Costa, M A; Monsalvo, R; Palenque, E; Costa, J R; Del, Palacio A

    2002-01-01

    Paradoxical worsening or relapse of opportunistic infections has been described after initiation of highly active anti-retroviral therapy (HAART) in human immunodeficiency virus (HIV) infected patients. Retrospective study of a group of 33 HIV-infected patients with mycobacterial disease analysing the incidence and characteristics of patients with and without paradoxical response after starting HAART and/or mycobacterial treatment. Nine patients in the group had paradoxical response. No significant difference of baseline characteristics was observed in these patients. The decrease in viral load was significantly greater among patients with paradoxical response than in patients without. No clinical difference was found in the evolution of HIV-infected patients with mycobacterial disease after the resolution of the episode of paradoxical response.

  5. HIV-1 Tropism Evolution after Short-Term Maraviroc Monotherapy in HIV-1-Infected Patients

    PubMed Central

    Gonzalez-Serna, Alejandro; Romero-Sánchez, María Concepción; Ferrando-Martinez, Sara; Genebat, Miguel; Vidal, Francesc; Muñoz-Fernández, Maria Ángeles; Abad, María Antonia

    2012-01-01

    We analyzed the evolution of viral tropism after 8 days of maraviroc monotherapy, i.e., we used the maraviroc clinical test (MCT), in 21 patients with and 14 without virological response to the drug (MCT+ and MCT− patients, respectively). No increases in CXCR4 inferred viral loads (X4IVLs) were observed in MCT+ patients, while X4IVLs increased only in MCT− patients, with X4IVLs of >2 log10 HIV RNA copies/ml. These results shed light on the evolution of viral tropism under a CCR5 antagonist in vivo. PMID:22547624

  6. Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study.

    PubMed

    Agüero, F; Rimola, A; Stock, P; Grossi, P; Rockstroh, J K; Agarwal, K; Garzoni, C; Barcan, L A; Maltez, F; Manzardo, C; Mari, M; Ragni, M V; Anadol, E; Di Benedetto, F; Nishida, S; Gastaca, M; Miró, J M

    2016-02-01

    Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  7. Role of telaprevir plasma levels for predicting response to antiviral therapy in patients with hepatitis C virus genotype 1 infection.

    PubMed

    Farnik, Harald; Ferreirós, Nerea; Labocha, Sandra; Geisslinger, Gerd; Zeuzem, Stefan; Sarrazin, Christoph; Vermehren, Johannes

    2014-12-01

    Telaprevir (TVR)-based triple therapy has substantially improved cure rates of hepatitis C virus (HCV) genotype 1 infection but side effects are frequent and often severe. Therefore, response predictors are needed for early identification of patients not responding to TVR-based triple therapy. Forty-five patients (mean age: 54 ± 13 years; male gender: 60%; treatment-experienced: 82%; cirrhosis: 58%) with HCV genotype 1 infection were treated with a TVR-based triple-therapy regimen. TVR plasma levels were analyzed by liquid chromatography electrospray-ionization-tandem mass spectrometry at weeks 2, 4, 8, and 12 of antiviral therapy. On-treatment HCV RNA response was assessed at weeks 4, 12, and 24 by real-time polymerase chain reaction. An extended rapid virological response (eRVR) and sustained virological response (SVR) was achieved in 21 of 45 patients (47%) and 36 of 45 (80%) patients, respectively. Mean ± standard deviation TVR plasma levels at week 2 were 3.4 ± 0.2 log10 ng/ml and did not differ over time (when assessed at weeks 4, 8, and 12). TVR plasma levels at week 2 were significantly higher in patients who achieved an eRVR compared to those who did not achieve eRVR (3.5 ± 0.1 vs. 3.3 ± 0.2 log10 ng/ml; p = 0.003) but were neither associated with SVR nor with treatment-related anemia. TVR plasma levels are associated with on-treatment response but not with overall treatment efficacy. Given the high overall response rates to TVR-based triple therapy, our data suggest that TVR trough levels may not be a useful predictor of treatment response, and routine drug-level monitoring is not required.

  8. Ability to Work and Employment Rates in Human Immunodeficiency Virus (HIV)-1-Infected Individuals Receiving Combination Antiretroviral Therapy: The Swiss HIV Cohort Study.

    PubMed

    Elzi, Luigia; Conen, Anna; Patzen, Annalea; Fehr, Jan; Cavassini, Matthias; Calmy, Alexandra; Schmid, Patrick; Bernasconi, Enos; Furrer, Hansjakob; Battegay, Manuel

    2016-01-01

    Background.  Limited data exist on human immunodeficiency virus (HIV)-infected individuals' ability to work after receiving combination antiretroviral therapy (cART). We aimed to investigate predictors of regaining full ability to work at 1 year after starting cART. Methods.  Antiretroviral-naive HIV-infected individuals <60 years who started cART from January 1998 through December 2012 within the framework of the Swiss HIV Cohort Study were analyzed. Inability to work was defined as a medical judgment of the patient's ability to work as 0%. Results.  Of 5800 subjects, 4382 (75.6%) were fully able to work, 471 (8.1%) able to work part time, and 947 (16.3%) were unable to work at baseline. Of the 947 patients unable to work, 439 (46.3%) were able to work either full time or part time at 1 year of treatment. Predictors of recovering full ability to work were non-white ethnicity (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20-3.54), higher education (OR, 4.03; 95% CI, 2.47-7.48), and achieving HIV-ribonucleic acid <50 copies/mL (OR, 1.83; 95% CI, 1.20-2.80). Older age (OR, 0.55; 95% CI, .42-.72, per 10 years older) and psychiatric disorders (OR, 0.24; 95% CI, .13-.47) were associated with lower odds of ability to work. Recovering full ability to work at 1 year increased from 24.0% in 1998-2001 to 41.2% in 2009-2012, but the employment rates did not increase. Conclusions.  Regaining full ability to work depends primarily on achieving viral suppression, absence of psychiatric comorbidity, and favorable psychosocial factors. The discrepancy between patients' ability to work and employment rates indicates barriers to reintegration of persons infected with HIV.

  9. Ability to Work and Employment Rates in Human Immunodeficiency Virus (HIV)-1-Infected Individuals Receiving Combination Antiretroviral Therapy: The Swiss HIV Cohort Study

    PubMed Central

    Elzi, Luigia; Conen, Anna; Patzen, Annalea; Fehr, Jan; Cavassini, Matthias; Calmy, Alexandra; Schmid, Patrick; Bernasconi, Enos; Furrer, Hansjakob; Battegay, Manuel

    2016-01-01

    Background. Limited data exist on human immunodeficiency virus (HIV)-infected individuals' ability to work after receiving combination antiretroviral therapy (cART). We aimed to investigate predictors of regaining full ability to work at 1 year after starting cART. Methods. Antiretroviral-naive HIV-infected individuals <60 years who started cART from January 1998 through December 2012 within the framework of the Swiss HIV Cohort Study were analyzed. Inability to work was defined as a medical judgment of the patient's ability to work as 0%. Results. Of 5800 subjects, 4382 (75.6%) were fully able to work, 471 (8.1%) able to work part time, and 947 (16.3%) were unable to work at baseline. Of the 947 patients unable to work, 439 (46.3%) were able to work either full time or part time at 1 year of treatment. Predictors of recovering full ability to work were non-white ethnicity (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.20–3.54), higher education (OR, 4.03; 95% CI, 2.47–7.48), and achieving HIV-ribonucleic acid <50 copies/mL (OR, 1.83; 95% CI, 1.20–2.80). Older age (OR, 0.55; 95% CI, .42–.72, per 10 years older) and psychiatric disorders (OR, 0.24; 95% CI, .13–.47) were associated with lower odds of ability to work. Recovering full ability to work at 1 year increased from 24.0% in 1998–2001 to 41.2% in 2009–2012, but the employment rates did not increase. Conclusions. Regaining full ability to work depends primarily on achieving viral suppression, absence of psychiatric comorbidity, and favorable psychosocial factors. The discrepancy between patients' ability to work and employment rates indicates barriers to reintegration of persons infected with HIV. PMID:26955645

  10. [Genotypic resistance in HIV-1-infected patients with persistent low-level viremia].

    PubMed

    Parra-Ruiz, Jorge; Alvarez, Marta; Chueca, Natalia; Peña, Alejandro; Pasquau, Juan; López-Ruz, Miguel Angel; Maroto, María Del Carmen; Hernández-Quero, José; García, Federico

    2009-02-01

    Highly active antiretroviral therapy (HAART) in HIV patients is considered successful when plasma viral load (VL) reaches < 50 copies/ml. However, many patients have a persistent VL of 50 to 1000 copies/ml, and treatment guidelines do not recommend genotypic resistance testing at these levels because of poor performance. The aim of this study was to evaluate the usefulness of a concentration technique for HIV-1 sequencing in samples with < 1000 copies/ml, and determine the virological consequences of HAART treatment changes guided by resistance testing in this scenario. Observational study performed in 51 patients with plasma VL between 50 and 1000 copies/m; 27 patients had these levels for at least 12 consecutive months. Prior to RNA extraction, virions were concentrated from 3-ml plasma samples and then genotyped following standard procedures. Forty-seven of the 51 samples were successfully sequenced, resulting in a sensitivity of 92%. Among these 47 patients, 27 showed a persistent viral load of 50-1000 copies/ml for 12 months, and 20 patients achieved undetectable viral load following the genotype-guided HAART change (intention-to-treat analysis: NC = F; 20 of 27 [74.1%]; on-treatment analysis: 20 of 23 [86.9%]). We report a simple method for genotype sequencing in patients with persistent low-level viremia that allowed a modification of the HAART regimen leading to undetectable plasma viremia.

  11. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients.

    PubMed

    Alvarez-Muñoz, Ma Teresa; Maldonado-Rodriguez, Angelica; Rojas-Montes, Othon; Torres-Ibarra, Rocio; Gutierrez-Escolano, Fernanda; Vazquez-Rosales, Guillermo; Gomez, Alejandro; Muñoz, Onofre; Torres, Javier; Lira, Rosalia

    2014-10-07

    To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson's χ(2) and/or Fisher's exact test. We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.

  12. Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

    PubMed Central

    Alvarez-Muñoz, Ma Teresa; Maldonado-Rodriguez, Angelica; Rojas-Montes, Othon; Torres-Ibarra, Rocio; Gutierrez-Escolano, Fernanda; Vazquez-Rosales, Guillermo; Gomez, Alejandro; Muñoz, Onofre; Torres, Javier; Lira, Rosalia

    2014-01-01

    AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson’s χ2 and/or Fisher’s exact test. RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV. PMID:25309083

  13. Poor functional immune recovery in aged HIV-1-infected patients following successfully treatment with antiretroviral therapy.

    PubMed

    Kasahara, Taissa M; Hygino, Joana; Andrade, Regis M; Monteiro, Clarice; Sacramento, Priscila M; Andrade, Arnaldo F B; Bento, Cleonice A M

    2015-10-01

    Aging is now a well-recognized characteristic of the HIV-infected population and both AIDS and aging are characterized by a deficiency of the T-cell compartment. The objective of the present study was to evaluate the impact of antiretroviral (ARV) therapy in recovering functional response of T cells to both HIV-1-specific ENV peptides (ENV) and tetanus toxoid (TT), in young and aged AIDS patients who responded to ARV therapy by controlling virus replication and elevating CD4(+) T cell counts. Here, we observed that proliferative response of T-cells to either HIV-1-specific Env peptides or tetanus toxoid (TT) was significantly lower in older antiretroviral (ARV)-treated patients. With regard to cytokine profile, lower levels of IFN-γ, IL-17 and IL-21, associated with elevated IL-10 release, were produced by Env- or TT-stimulated T-cells from older patients. The IL-10 neutralization by anti-IL-10 mAb did not elevate IFN-γ and IL-21 release in older patients. Finally, even after a booster dose of TT, reduced anti-TT IgG titers were quantified in older AIDS patients and it was related to both lower IL-21 and IFN-γ production and reduced frequency of central memory T-cells. Our results reveal that ARV therapy, despite the adequate recovery of CD4(+) T cell counts and suppression of viremia, was less efficient in recovering adequate immune response in older AIDS patients.

  14. Excessive early mortality in the first year of treatment in HIV type 1-infected patients initiating antiretroviral therapy in resource-limited settings.

    PubMed

    Marazzi, Maria Cristina; Liotta, Giuseppe; Germano, Paola; Guidotti, Giovanni; Altan, A Doro; Ceffa, Susanna; Lio, Massimo Magnano San; Nielsen-Saines, Karin; Palombi, Leonardo

    2008-04-01

    The response to treatment and risk factors for early mortality following initiation of combination antiretrovirals(ARVs) in a cohort of African patients are described in a retrospective cohort design. Medical history, laboratory parameters, and mortality data were reviewed for patients initiating ARVs in 12 clinical centers in Mozambique, Tanzania, and Malawi. Among 3456 HIV-1-infected patients who received ARVs for more than 6 months, at baseline 72% had WHO clinical stages 3/4, 7% had a viral load 400 copies/ml, and 38% had a CD4 cell count >200/microl. One year later, 78% had undetectable virus loads and 79% had CD4 cell counts >200 cells/mm3. In the first year of HAART 260 deaths occurred (97 per 1000 person/years) with mortality peaking in the first 3 months. The highest mortality was observed in patients with low BMI, low hemoglobin levels, and CD4 values <200 cells/microl at baseline. Mortality rates following initiation of HAART are higher in patients in resource-limited areas, particularly in the first 90 days following treatment initiation.HAART initiated at higher CD4 cell count levels, especially among malnourished and/or anemic patients, will carry significant public health impact.

  15. Static and dynamic posturography in patients with asymptomatic HIV-1 infection and AIDS

    PubMed Central

    Dellepiane, M; Medicina, MC; Mora, R; Salami, A

    2005-01-01

    Summary Alterations of the vestibulo-ocular reflex, optokinetic nystagmus, and visuo-vestibular-ocular reflex, have already been described in patients with AIDS and HIV-1 positive asymptomatic subjects. The introduction to the clinical practice of posturographic techniques allows us to study, with precision, postural perturbation that may be present when performing Romberg’s test and to study the vestibulo-spinal reflex as a component of the vestibular system. The relative lack of studies on posturography and AIDS, encouraged us to continue our research on the vestibular system both in asymptomatic HIV-1 seropositive patients and in patients with AIDS (IV stage according to the classification proposed by the Centre for Disease Control). Recordings were made in group 1 (control group, 55 normal subjects), in group 2 (15 asymptomatic HIV-positive subjects), and in group 3 (15 patients with AIDS stage IV). Static and dynamic posturography were carried out using Tonnies platform system (Tonnies GmbH & Co., Wurzburg, Germany) and the data were analysed with Tonnies Posturographic Tübingen (TPOST) software vers. 5.19. In asymptomatic HIV+ subjects, we observed an increase in RW, RA and M3 reflex latency. AIDS patients (stage IV) exhibited significant alterations in almost all the posturographic parameters and the electromyographic potentials. Our results validate static and dynamic posturography as a method for otoneurological investigation and appear to confirm that the entire vestibular system is involved since the earliest stages of the HIV infection. In the HIV+ subjects, a variable dysfunction in the reflex control to long latency was observed, which is correlated with the alteration of the central dopaminergic system; in AIDS patients, the central nervous system damage appears more important, globally distributed and correlated also with immunosuppression. PMID:16749603

  16. Hypotension in ICU Patients Receiving Vasopressor Therapy.

    PubMed

    Yapps, Bryce; Shin, Sungtae; Bighamian, Ramin; Thorsen, Jill; Arsenault, Colleen; Quraishi, Sadeq A; Hahn, Jin-Oh; Reisner, Andrew T

    2017-08-17

    Vasopressor infusion (VPI) is used to treat hypotension in an ICU. We studied compliance with blood pressure (BP) goals during VPI and whether a statistical model might be efficacious for advance warning of impending hypotension, compared with a basic hypotension threshold alert. Retrospective data were obtained from a public database. Studying adult ICU patients receiving VPI at submaximal dosages, we analyzed characteristics of sustained hypotension episodes (>15 min) and then developed a logistic regression model to predict hypotension episodes using input features related to BP trends. The model was then validated with prospective data. In the retrospective dataset, 102-of-215 ICU stays experienced >1 hypotension episode (median of 2.5 episodes per day in this subgroup). When trained with 75% of retrospective dataset, testing with the remaining 25% of the dataset showed that the model and the threshold alert detected 99.6% and 100% of the episodes, respectively, with median advance forecast times (AFT) of 12 and 0 min. In a second, prospective dataset, the model detected 100% of 26 episodes with a median AFT of 22 min. In conclusion, episodes of hypotension were common during VPI in the ICU. A logistic regression model using BP temporal trend features predicted the episodes before their onset.

  17. The anemia prevalence and the association between complete blood count analysis and renal function parameters in HIV-1-infected patients.

    PubMed

    Dabrowska, Magdalena M; Mikula, Tomasz; Wiercinska-Drapalo, Alicja

    2012-04-01

    To determine the anemia prevalence and the correlation between complete blood count (CBC) analysis and renal function parameters in HIV-1-infected population. It was a single-center study set in Warsaw (Poland) over a 3-year period. The study was performed in 214 adult HIV-1- infected patients (180 males and 34 females, aged from 20 to 69 years old, mean age 39.55 years, 130 on combined antiretroviral therapy, cART). Glomerular filtration rate (GFR) was estimated using the re-expressed Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. In statistical analyses U Mann-Whitney and Spearman correlation test as logistic regression analysis was used. 25.2% of studied patients were anemic. In all of them, estimated GFR (eGFR) was positively correlated with red blood cells (RBC) and platelet (PLT) count, and negatively correlated with mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC). All these correlations were statistically significant (p < 0.001) and independent of gender and used type of eGFR formula. In logistic regression analysis, lower eGFR strongly predicted lower RBC and PLT levels (p < 0.0001; OR 0.08, 95%CI: 0.03, 0.22 and OR 0.99, 95%CI: 0.987, 0.993, respectively). Our findings suggest a strong association between CBC and renal function in ARV-treated HIV-infected patients who fulfilled the criteria of anemia. Consequently, eGFR in all HIV-infected subjects with anemia, especially on treatment with nephrotoxic drugs and concomitant thrombocytopenia, should be monitored more frequently then standardly recommended every 3-6 months.

  18. Recurrent intraoral HSV-1 infection: A retrospective study of 58 immunocompetent patients from Eastern Europe.

    PubMed

    Tovaru, Serban; Parlatescu, Ioanina; Tovaru, Mihaela; Cionca, Lucia; Arduino, Paolo-Giacomo

    2011-03-01

    To revise the clinical features of the recurrent intraoral herpetic infection (RIOH) with respect to precipitating factors, demographic, clinical features and outcome. Fifty-eight, unrelated Caucasian, immunocompetent patients with positive laboratory test for intraoral Herpes simplex virus infection were studied. The mean age in the women's group (n=42) was 41.23 years (± 21.73) and in the men's group was 32.25 years (±15.68). Possible trigger factors were identified in 9 cases (15.5%). General symptoms were noted in 20 cases (34.48%). Most of patients in this study presented multiple lesions. 14 patients had vermillion lesions associated with intraoral lesions. In most of the cases both fixed and mobile mucosa was concomitantly involved. Treatment was prescribed in order to control the symptoms and to shorten the evolution with minimal side effects. Intraoral secondary herpetic infection could be polymorphous and sometimes associated with general symptoms. The recognition of its atypical features may prevent unnecessary and costly investigations and treatments for unrelated though clinically similar-appearing disorders.

  19. Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and FcγRIIa polymorphism characteristics

    PubMed Central

    Payeras, A; Martinez, P; Milà, J; Riera, M; Pareja, A; Casal, J; Matamoros, N

    2002-01-01

    The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment. Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines. Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG2m and FcγRIIa allotypes were determined. A history of drug abuse (P = 0·001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0·01), higher levels of HIV-1 viral load (P < 0·05), serum IgG (P < 0·01) and beta2-microglobulin (P < 0·01) were observed in the case group. Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups. No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG2m and FcγRIIa allotypes between the three groups. These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered. PMID:12390315

  20. [Association of PD-1 expression on CD4+ CD25 nt/hi CD127 lo regulatory T cells with disease progression in HIV-1 infected patients].

    PubMed

    Cao, Qing-hua; Xue, Yi-le; Wang, Ying

    2009-11-01

    To investigate whether Programmed death-1 (PD-1) expression on peripheral CD4(+)CD25(nt/hi)CD127(lo) regulatory T cells (Treg) was associated with disease progression in HIV-1-infected patients. Peripheral blood from 108 HIV-1-infected patients in distinct disease progression statuses and 27 healthy individuals were collected in the present investigation. PBMCs were isolated by centrifugation on Ficoll-Hypaque, followed by staining with anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE and anti-PD-1-APC. PD-1 expression on Treg was analyzed by four-color staining flow cytometry. CD4(+) T cell absolute counts were determined using Multitest CD3/CD4/CD8/CD45 kit and plasma viral loads were detected on NucliSens EasyQ. All data were analyzed using SPSS14.0 software. In peripheral blood of healthy individuals, Treg expressed PD-1 at very low levels (1.72%+/-0.65%). In contrast, Treg from HIV-1-infected patients showed a significantly increased PD-1 expression (5.33%+/-2.24%, P<0.01). Moreover, AIDS patients exhibited statistically higher PD-1 expression on Treg (7.87%+/-2.23%) than newly HIV-1 infected patients (3.22%+/-1.01%, P<0.05) and patients in progression to AIDS(5.21%+/-1.72%, P<0.05). PD-1 up-regulation on Treg was closely correlated with reduced CD4(+) T cell absolute counts but elevated plasma viral load. Overall, we found that PD-1 expression on peripheral Treg was up-regulated and correlated with disease progression in HIV-1-infected patients for the first time. These findings not only extend our understanding of how Treg functions in HIV-1-infected patients but also support the notion that blocking PD-1/PD-L1 interactions may represent a potential therapeutic strategy for HIV-1-infected patients.

  1. Evolution of resistance to drugs in HIV-1-infected patients failing antiretroviral therapy

    PubMed Central

    Kantor, Rami; Shafer, Robert W.; Follansbee, Stephen; Taylor, Jonathan; Shilane, David; Hurley, Leo; Nguyen, Dong-Phuong; Katzenstein, David; Fessel, W. Jeffrey

    2008-01-01

    Background and objective The optimal time for changing failing antiretroviral therapy (ART) is not known. It involves balancing the risk of exhausting future treatment options against the risk of developing increased drug resistance. The frequency with which new drug-resistance mutations (DRM) developed and their potential consequences in patients continuing unchanged treatment despite persistent viremia were assessed. Design A retrospective study of consecutive sequence samples from 106 patients at one institution with viral load (VL) of more than 400 copies/ml, with no change in ART for more than 2 months despite virologic failure. Methods Two consecutive pol sequences, CD4 cell counts and VL were analyzed to quantify the development of new DRM and to identify changes in immunologic and virologic parameters. Genotypic susceptibility scores (GSS) and viral drug susceptibilities were calculated by a computer program (HIVDB). Poisson log-linear regression models were used to predict the expected number of mutations at the second time point. Results After a median of 14 months of continued ART, 75% (80 of 106) of patients acquired new DRM and were assigned a significantly lower GSS, potentially limiting the success of future ART. The development of new DRM was proportional to the time between the two sequences and inversely proportional to the number of DRM in the first sequence. However, the development of DRM was not associated with significant changes in CD4 or VL counts. Conclusions Despite stable levels of CD4 and VL over time, maintaining a failing therapeutic regimen increases drug resistance and may limit future treatment options. PMID:15238768

  2. Increased Intrathecal Immune Activation in Virally Suppressed HIV-1 Infected Patients with Neurocognitive Impairment

    PubMed Central

    Edén, Arvid; Marcotte, Thomas D.; Heaton, Robert K.; Nilsson, Staffan; Zetterberg, Henrik; Fuchs, Dietmar; Franklin, Donald; Price, Richard W.; Grant, Igor; Letendre, Scott L.; Gisslén, Magnus

    2016-01-01

    Objective Although milder forms of HIV-associated neurocognitive disorder (HAND) remain prevalent, a correlation to neuronal injury has not been established in patients on antiretroviral therapy (ART). We examined the relationship between mild HAND and CSF neurofilament light protein (NFL), a biomarker of neuronal injury; and CSF neopterin, a biomarker of CNS immunoactivation, in virally suppressed patients on antiretroviral therapy (ART). Design and Methods We selected 99 subjects on suppressive ART followed longitudinally from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Based on standardized comprehensive neurocognitive performance (NP) testing, subjects were classified as neurocognitively normal (NCN; n = 29) or impaired (NCI; n = 70). The NCI group included subjects with asymptomatic (ANI; n = 37) or mild (MND; n = 33) HAND. CSF biomarkers were analyzed on two occasions. Results Geometric mean CSF neopterin was 25% higher in the NCI group (p = 0.04) and NFL and neopterin were significantly correlated within the NCI group (r = 0.30; p<0.001) but not in the NCN group (r = -0.13; p = 0.3). Additionally, a trend towards higher NFL was seen in the NCI group (p = 0.06). Conclusions Mild HAND was associated with increased intrathecal immune activation, and the correlation between neopterin and NFL found in NCI subjects indicates an association between neurocognitive impairment, CNS inflammation and neuronal damage. Together these findings suggest that NCI despite ART may represent an active pathological process within the CNS that needs further characterization in prospective studies. PMID:27295036

  3. [Analysis of serum neutralizing antibody response in patients with primary dengue virus type 1 infection].

    PubMed

    Hu, Dongmei; Li, Jie; Wang, Dahu; DI, Biao; Qiu, Liwen; Wang, Yadi; Ding, Xixia; Che, Xiaoyan

    2012-12-01

    To investigate the characteristics and dynamic changes of serum neutralizing antibody response in patients with primary infection of dengue virus type 1 (DENV-1). Serum samples were obtained from the same patients with primary infection of DENV-1 within 2 weeks after symptom onset in 2006 and in 2010. A group-specific DENV NS1 capture ELISA-based micro-neutralizing test (ELISA-MNT) capable of detecting neutralizing antibodies against all the 4 serotypes of DENV was used to test the neutralizing antibody titers against DENV in the serum samples. The neutralizing antibody titers against a standard strain and 2 clinically isolated strains of DENV-1 were detected in serum samples collected in 2010. Cross-reactive neutralizing antibody response against all the 4 serotypes of DENV was found in both of the serum samples collected in 2006 and 2010, but the samples collected in 2006 showed stronger cross-reactive neutralizing antibody responses. The neutralizing antibody against DENV-2, rather than the anticipated DENV-1 antibody, had the highest titer in the samples collected in 2006, whereas the antibody against homologous DENV-1 had the highest titer in the samples obtained in 2010. The neutralizing antibody titers against the homologous DENV-1 was significantly higher in samples collected in 2010 (U=86.500, P=0.000), which also demonstrated significantly different neutralizing antibody titers against the 3 different strains of DENV-1 (Χ(2)=12.123, P=0.002). The production of cross-reactive neutralizing antibodies between the 4 serotypes of DENV is a characteristic of DENV infection, particularly during early infection, but only the homologous neutralizing antibody increases obviously over time. The titers of the neutralizing antibodies against different strains, even of the same serotype, may differ distinctly.

  4. Correlation between resistance profile and immunosuppression in heavily treated HIV-1 infected Romanian patients

    PubMed Central

    Manolescu, Loredana; Temereanca, Aura; Diaconu, Carmen Cristina; Ruta, Simona

    2011-01-01

    Background and Objective As available data on HIV-1 strains from Romania indicate the prevalence of a particular subtype- F, not found in other European countries, we aimed at investigating the impact on drug susceptibility of mutations associated with drug resistance and their correlation with the virological and immune response to therapy. Methods 38 long term survivors, HIV-1 parenterally infected in childhood, with repeated virological failures, were genotyped for drug resistance and subtype determination. A phylogenetic tree of aligned reversetranscriptase sequences was built. Results 94.7% of all the patients’strains were subtype F1, clustering together with other Romanian and Angolan F1 strains. Despite the long and complex treatments, 15.8% of patients had wild type virus, 68.4% were fully susceptible to protease inhibitors, 47.3% to non-nucleoside reverstranscriptase inhibitors, 28.9% to nucleoside reverstranscriptase inhibitors. Only 13.2% were resistant to all antiretroviral drug classes. A significantly higher total number of mutations were encountered in severely immunosuppressed patients, who presented also major mutations in the protease gene (V82A, I54V, G48V) and the major M184V mutation associated with type 2 thymidine analogs mutations in reverstranscriptase gene. Conclusion A good immune status seems to be associated with a low range of mutations, indicating the impact of immune restoration or preservation on the therapeutic success rate. The slower post-HAART progression of mutational pattern of HIV- 1 subtype F1 in long term survivors may also influence the viral replicative fitness, a fact that can explain its steady prevalence in Romania. PMID:22180722

  5. Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

    PubMed Central

    Ruiz-Valderas, Rosa; Sánchez-Rivas, Elena; Lluch, Amparo; Gutierrez-Valencia, Alicia; Torres-Cornejo, Almudena; BenMarzouk-Hidalgo, Omar J.; Viciana, Pompeyo

    2013-01-01

    There is significant intra- and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI95], 75.3 to 89.3%). Virological efficacy was independent of LPV plasma concentrations even when LPVr was given once daily. An adherence of <90% (HR, 4.4 [CI95, 1.78 to 10.8; P = 0.001]) and the presence of blips in the preceding 12 months (HR, 3.06 [CI95, 1.17 to 8.01; P = 0.022]) were the only variables independently associated with time to VF. These findings suggest that the LPV concentrations achieved with the standard doses of LPVr are sufficient to maintain virological control during monotherapy and that measurement of LPV concentrations is not useful for predicting virological outcome. Tight control of viral replication in the previous months and strict adherence throughout the mtLPVr regimen could improve the virological efficacy of this maintenance regimen. PMID:23716055

  6. Effect of Integrated Yoga (IY) on psychological states and CD4 counts of HIV-1 infected patients: A randomized controlled pilot study

    PubMed Central

    Naoroibam, Rosy; Metri, Kashinath G; Bhargav, Hemant; Nagaratna, R; Nagendra, HR

    2016-01-01

    Background: Human immunodeficiency virus (HIV) infected individuals frequently suffer from anxiety and depression. Depression has been associated with rapid decline in CD4 counts and worsened treatment outcomes in HIV-infected patients. Yoga has been used to reduce psychopathology and improve immunity. Aim: To study the effect of 1-month integrated yoga (IY) intervention on anxiety, depression, and CD4 counts in patients suffering from HIV-1 infection. Methods: Forty four HIV-1 infected individuals from two HIV rehabilitation centers of Manipur State of India were randomized into two groups: Yoga (n = 22; 12 males) and control (n = 22; 14 males). Yoga group received IY intervention, which included physical postures (asanas), breathing practices (pranayama), relaxation techniques, and meditation. IY sessions were given 60 min/day, 6 days a week for 1 month. Control group followed daily routine during this period. All patients were on anti-retroviral therapy (ART) and dosages were kept stable during the study. There was no significant difference in age, gender, education, CD4 counts, and ART status between the two groups. Hospital anxiety and depression scale was used to assess anxiety and depression, CD4 counts were measured by flow cytometry before and after intervention. Analysis of variance – repeated measures was applied to analyze the data using SPSS version 10. Results: Within group comparison showed a significant reduction in depression scores (F [1, 21] =4.19, P < 0.05) and non-significant reduction in anxiety scores along with non significant increment in CD4 counts in the yoga group. In the control group, there was a non-significant increase in anxiety and depression scores and reduction in CD4 counts. Between-group comparison revealed a significant reduction in depression scores (F [1, 21] =5.64, P < 0.05) and significant increase in CD4 counts (F [1, 21] =5.35, P < 0.05) in the yoga group as compared to the control. Conclusion: One month practice of IY

  7. Serum levels of IgG antibodies against oxidized LDL and atherogenic indices in HIV-1-infected patients treated with protease inhibitors.

    PubMed

    da Cunha, Joel; Ferreira Maselli, Luciana Morganti; Treitinger, Arício; Monteiro, Andrea Moreira; Gidlund, Magnus; Maranhão, Raul Cavalcanti; Spada, Celso; Bydlowski, Sérgio Paulo

    2013-02-01

    Antibodies against low-density lipoproteins (LDLs) that have been oxidized are associated with development of atherosclerotic lesions. In individuals infected with human immunodeficiency virus type 1 (HIV-1) with or without therapy, dyslipidemia and increased cardiovascular risk are observed. Serum levels of IgG antibodies against oxidized LDLs (IgG anti-oxLDL Abs) were determined by assay in 151 HIV-1-infected patients. Of these, 42 patients did not receive anti-retroviral therapy (ART-naïve), whereas 109 received highly active anti-retroviral therapy (HAART) consisting of lopinavir/ritonavir (LOP/r; n=50), efavirenz (EFV; n=30) and nevirapine (NVP; n=29) associated with nucleoside reverse transcriptase inhibitors. HIV-1 seronegative individuals (n=43) participated in the study. The following parameters were quantified: total cholesterol and its fractions, atherogenic indices (AIs), apolipoproteins A1 and B100, high sensitivity C-reactive protein, CD4+ and CD8+ T cells, and HIV-1-RNA. Levels of IgG anti-oxLDL Abs were significantly higher (p<0.05) in the LOP/r group compared with the EFV and/or NVP and the seronegative group: median 0.32 (0.15, 0.58; 95% confidence interval) vs. 0.25 (0.13, 0.53) vs. 0.18 (0.04, 0.38), respectively. HIV-1-infected ART-naïve patients (n=42) presented antibodies levels similar to those observed for the LOP/r group, 0.33 (0.13, 0.63; p>0.05). The levels of IgG anti-oxLDL Abs correlated with an increase in AIs (r=0.216; p=0.036) and triglycerides (r=0.220; p=0.044) in the LOP/r group, and AIs in the ART-naïve group (r=0.300; p=0.046). Patients treated with LOP/r showed higher levels of IgG anti-oxLDL Abs compared with patients treated with EFV or NVP regimens, and these levels were associated with an increase in AIs.

  8. Effects of once-daily darunavir/ritonavir versus lopinavir/ritonavir on metabolic parameters in treatment-naive HIV-1-infected patients at week 96: ARTEMIS.

    PubMed

    Arathoon, E; Schneider, S; Baraldi, E; Lim, P L; Opravil, M; Van De Casteele, T; Lavreys, L

    2013-01-01

    In the ARTEMIS trial, 689 treatment-naïve, HIV-1-infected adults received darunavir/ritonavir (DRV/r) 800/100 mg every day or lopinavir/ritonavir (LPV/r) 800/200 mg total daily dose plus fixed-dose tenofovir/emtricitabine. Week 96 metabolic parameters are reported. Adverse events (AEs) classed as metabolism/nutrition disorders were observed in 14% of DRV/r and 22% of LPV/r patients. Lipid-related AEs were reported in fewer DRV/r (8%) than LPV/r (16%) patients. A small increase in glucose and insulin levels was observed at week 96 in both groups. Lipoma was the only lipodystrophy-related AE reported in >1% of patients (DRV/r, n = 1; LPV/r, n = 4) and no grade 3 or 4 lipodystrophy-related AEs were reported. No clinically relevant changes from baseline were seen in anthropometric measurements in either group. Median mid-waist/hip ratio at week 96 was comparable to baseline in both arms. Over 96 weeks, DRV/r had a similar effect on glucose and insulin levels but a more favourable lipid profile than LPV/r in treatment-naïve, HIV-infected patients.

  9. Low Prevalence of Transmitted Drug Resistance in Patients Newly Diagnosed with HIV-1 Infection in Sweden 2003–2010

    PubMed Central

    Karlsson, Annika; Björkman, Per; Bratt, Göran; Ekvall, Håkan; Gisslén, Magnus; Sönnerborg, Anders; Mild, Mattias; Albert, Jan

    2012-01-01

    Transmitted drug resistance (TDR) is a clinical and epidemiological problem because it may contribute to failure of antiretroviral treatment. The prevalence of TDR varies geographically, and its prevalence in Sweden during the last decade has not been reported. Plasma samples from 1,463 patients newly diagnosed with HIV-1 infection between 2003 and 2010, representing 44% of all patients diagnosed in Sweden during this period, were analyzed using the WHO 2009 list of mutations for surveillance of TDR. Maximum likelihood phylogenetic analyses were used to determine genetic subtype and to investigate the relatedness of the sequences. Eighty-two patients showed evidence of TDR, representing a prevalence of 5.6% (95% CI: 4.5%–6.9%) without any significant time trends or differences between patients infected in Sweden or abroad. Multivariable logistic regression showed that TDR was positively associated with men who have sex with men (MSM) and subtype B infection and negatively associated with CD4 cell counts. Among patients with TDR, 54 (68%) had single resistance mutations, whereas five patients had multi-drug resistant HIV-1. Phylogenetic analyses identified nine significantly supported clusters involving 29 of the patients with TDR, including 23 of 42 (55%) of the patients with TDR acquired in Sweden. One cluster contained 18 viruses with a M41L resistance mutation, which had spread among MSM in Stockholm over a period of at least 16 years (1994–2010). Another cluster, which contained the five multidrug resistant viruses, also involved MSM from Stockholm. The prevalence of TDR in Sweden 2003–2010 was lower than in many other European countries. TDR was concentrated among MSM, where clustering of TDR strains was observed, which highlights the need for continued and improved measures for targeted interventions. PMID:22448246

  10. Predicted residual activity of rilpivirine in HIV-1 infected patients failing therapy including NNRTIs efavirenz or nevirapine.

    PubMed

    Theys, K; Camacho, R J; Gomes, P; Vandamme, A M; Rhee, S Y

    2015-06-01

    Rilpivirine is a second-generation nonnucleoside reverse-transcriptase inhibitor (NNRTI) currently indicated for first-line therapy, but its clinical benefit for HIV-1 infected patients failing first-generation NNRTIs is largely undefined. This study quantified the extent of genotypic rilpivirine resistance in viral isolates from 1212 patients upon failure of efavirenz- or nevirapine-containing antiretroviral treatment, of whom more than respectively 80% and 90% showed high-level genotypic resistance to the failing NNRTI. Of all study patients, 47% showed a rilpivirine resistance-associated mutation (RPV-RAM), whereas preserved residual rilpivirine activity was predicted in half of the patients by three genotypic drug resistance interpretation algorithms. An NNRTI-dependent impact on rilpivirine resistance was detected. Compared with the use of nevirapine, the use of efavirenz was associated with a 32% lower risk of having a RPV-RAM and a 50% lower risk of predicted reduced rilpivirine susceptibility. Most prevalent RPV-RAMs after nevirapine experience were Y181C and H221Y, whereas L100I+K103N, Y188L and K101E occurred most in efavirenz-experienced patients. Predicted rilpivirine activity was not affected by HIV-1 subtype, although frequency of individual mutations differed across subtypes. In conclusion, this genotypic resistance analysis strongly suggests that the latest NNRTI, rilpivirine, may retain activity in a large proportion of HIV-1 patients in whom resistance failed while they were on an efavirenz- or nevirapine-containing regimen, and may present an attractive option for second-line treatment given its good safety profile and dosing convenience. However, prospective clinical studies assessing the effectiveness of rilpivirine for NNRTI-experienced patients are warranted to validate knowledge derived from genotypic and phenotypic drug resistance studies.

  11. Yield of yearly routine physical examination in HIV-1 infected patients is limited: A retrospective cohort study in the Netherlands

    PubMed Central

    van Amsterdam, Marleen A.; van Assen, Sander; Sprenger, Herman G.; Wilting, Kasper R.; Stienstra, Ymkje

    2017-01-01

    Background Routine physical examinations might be of value in HIV-infected patients, but the yield is unknown. We determined the diagnoses that would have been missed without performing annual routine physical examinations in HIV-infected patients with stable disease. Methods Data were collected from the medical records of 299 HIV-1-infected patients with CD4 count >350 cells/mm3 if not using combination antiretroviral therapy (cART), or CD4 count >100 cells/mm3 and undetectable viral load if using cART. We defined the diagnoses that would have been missed without performing routine physical examinations on annual check-ups in 2010. Exclusion criteria were hepatitis B/C co-infection, start/ switch of cART < 24 weeks, pregnancy, and transgenderism. Results 215 patients (72%) had positive findings: lipodystrophy (30%), lymphadenopathy (16%) and hypertension (8.4%) were the most common. Two-thirds of all findings were not new or were based on complaints indicating a physical examination even if not routinely scheduled. For 24 patients (8.0%) the routine physical examination led to the finding of a new diagnosis: six—all men who have sex with men (MSM)—had a concurrent sexually transmitted infection, eight had hypertension, and ten others had a large variety of diagnoses. A total atrioventricular block with bradycardia was the most clinically relevant finding. Conclusions Annual physical examinations of HIV-infected patients with stable disease brought few new diagnoses that would have been missed without performing a routine examination. Our results suggest that standard assessments could be restricted to six-monthly measuring blood pressure in all patients and annually performing anogenital and digital rectal examination on MSM. PMID:28636651

  12. Yield of yearly routine physical examination in HIV-1 infected patients is limited: A retrospective cohort study in the Netherlands.

    PubMed

    van Amsterdam, Marleen A; van Assen, Sander; Sprenger, Herman G; Wilting, Kasper R; Stienstra, Ymkje; Bierman, Wouter F W

    2017-01-01

    Routine physical examinations might be of value in HIV-infected patients, but the yield is unknown. We determined the diagnoses that would have been missed without performing annual routine physical examinations in HIV-infected patients with stable disease. Data were collected from the medical records of 299 HIV-1-infected patients with CD4 count >350 cells/mm3 if not using combination antiretroviral therapy (cART), or CD4 count >100 cells/mm3 and undetectable viral load if using cART. We defined the diagnoses that would have been missed without performing routine physical examinations on annual check-ups in 2010. Exclusion criteria were hepatitis B/C co-infection, start/ switch of cART < 24 weeks, pregnancy, and transgenderism. 215 patients (72%) had positive findings: lipodystrophy (30%), lymphadenopathy (16%) and hypertension (8.4%) were the most common. Two-thirds of all findings were not new or were based on complaints indicating a physical examination even if not routinely scheduled. For 24 patients (8.0%) the routine physical examination led to the finding of a new diagnosis: six-all men who have sex with men (MSM)-had a concurrent sexually transmitted infection, eight had hypertension, and ten others had a large variety of diagnoses. A total atrioventricular block with bradycardia was the most clinically relevant finding. Annual physical examinations of HIV-infected patients with stable disease brought few new diagnoses that would have been missed without performing a routine examination. Our results suggest that standard assessments could be restricted to six-monthly measuring blood pressure in all patients and annually performing anogenital and digital rectal examination on MSM.

  13. Cost-effectiveness of boceprevir in patients previously treated for chronic hepatitis C genotype 1 infection in the United States.

    PubMed

    Chhatwal, Jagpreet; Ferrante, Shannon A; Brass, Cliff; El Khoury, Antoine C; Burroughs, Margaret; Bacon, Bruce; Esteban-Mur, Rafael; Elbasha, Elamin H

    2013-01-01

    The phase 3 trial, Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol-2 (RESPOND-2), demonstrated that the addition of boceprevir (BOC) to peginterferon-ribavirin (PR) resulted in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection as compared with PR alone. We evaluated the cost-effectiveness of treatment with BOC in previously treated patients with chronic hepatitis C in the United States using treatment-related data from RESPOND-2 and PROVIDE studies. We developed a Markov cohort model to project the burden of HCV disease, lifetime costs, and quality-adjusted life-years associated with PR and two BOC-based therapies-response-guided therapy (BOC/RGT) and fixed-duration therapy for 48 weeks (BOC/PR48). We estimated treatment-related inputs (efficacy, adverse events, and discontinuations) from clinical trials and obtained disease progression rates, costs, and quality-of-life data from published studies. We estimated the incremental cost-effectiveness ratio (ICER) for BOC-based regimens as studied in RESPOND-2, as well as by patient's prior response to treatment and the IL-28B genotype. BOC-based regimens were projected to reduce the lifetime incidence of liver-related complications by 43% to 53% in comparison with treatment with PR. The ICER of BOC/RGT in comparison with that of PR was $30,200, and the ICER of BOC/PR48 in comparison with that of BOC/RGT was $91,500. At a willingness-to-pay threshold of $50,000, the probabilities of BOC/RGT and BOC/PR48 being the preferred option were 0.74 and 0.25, respectively. In patients previously treated for chronic HCV genotype-1 infection, BOC was projected to increase quality-adjusted life-years and reduce the lifetime incidence of liver complications. In addition, BOC-based therapies were projected to be cost-effective in comparison with PR alone at commonly used willingness-to-pay thresholds. Copyright © 2013

  14. A model of HIV-1 infection with two time delays: mathematical analysis and comparison with patient data.

    PubMed

    Pawelek, Kasia A; Liu, Shengqiang; Pahlevani, Faranak; Rong, Libin

    2012-01-01

    Mathematical models have made considerable contributions to our understanding of HIV dynamics. Introducing time delays to HIV models usually brings challenges to both mathematical analysis of the models and comparison of model predictions with patient data. In this paper, we incorporate two delays, one the time needed for infected cells to produce virions after viral entry and the other the time needed for the adaptive immune response to emerge to control viral replication, into an HIV-1 model. We begin model analysis with proving the positivity and boundedness of the solutions, local stability of the infection-free and infected steady states, and uniform persistence of the system. By developing a few Lyapunov functionals, we obtain conditions ensuring global stability of the steady states. We also fit the model including two delays to viral load data from 10 patients during primary HIV-1 infection and estimate parameter values. Although the delay model provides better fits to patient data (achieving a smaller error between data and modeling prediction) than the one without delays, we could not determine which one is better from the statistical standpoint. This highlights the need of more data sets for model verification and selection when we incorporate time delays into mathematical models to study virus dynamics.

  15. A model of HIV-1 infection with two time delays: mathematical analysis and comparison with patient data

    PubMed Central

    Pawelek, Kasia A.; Liu, Shengqiang; Pahlevani, Faranak; Rong, Libin

    2011-01-01

    Mathematical models have made considerable contributions to our understanding of HIV dynamics. Introducing time delays to HIV models usually brings challenges to both mathematical analysis of the models and comparison of model predictions with patient data. In this paper, we incorporate two delays, one the time needed for infected cells to produce virions after viral entry and the other the time needed for the adaptive immune response to emerge to control viral replication, into an HIV-1 model. We begin model analysis with proving the positivity and boundedness of the solutions, local stability of the infection-free and infected steady states, and uniform persistence of the system. By developing a few Lyapunov functionals, we obtain conditions ensuring global stability of the steady states. We also fit the model including two delays to viral load data from 10 patients during primary HIV-1 infection and estimate parameter values. Although the delay model provides better fits to patient data (achieving a smaller error between data and modeling prediction) than the one without delays, we could not determine which one is better from the statistical standpoint. This highlights the need of more data sets for model verification and selection when we incorporate time delays into mathematical models to study virus dynamics. PMID:22108296

  16. Three-year safety and efficacy of vicriviroc, a CCR5 antagonist, in HIV-1-infected treatment-experienced patients.

    PubMed

    Wilkin, Timothy J; Su, Zhaohui; Krambrink, Amy; Long, Jianmin; Greaves, Wayne; Gross, Robert; Hughes, Michael D; Flexner, Charles; Skolnik, Paul R; Coakley, Eoin; Godfrey, Catherine; Hirsch, Martin; Kuritzkes, Daniel R; Gulick, Roy M

    2010-08-01

    Vicriviroc, an investigational CCR5 antagonist, demonstrated short-term safety and antiretroviral activity. Phase 2, double-blind, randomized study of vicriviroc in treatment-experienced subjects with CCR5-using HIV-1. Vicriviroc (5, 10, or 15 mg) or placebo was added to a failing regimen with optimization of background antiretroviral medications at day 14. Subjects experiencing virologic failure and subjects completing 48 weeks were offered open-label vicriviroc. One hundred eighteen subjects were randomized. Virologic failure (<1 log10 decline in HIV-1 RNA > or =16 weeks postrandomization) occurred by week 48 in 24 of 28 (86%), 12 of 30 (40%), 8 of 30 (27%), 10 of 30 (33%) of subjects randomized to placebo, 5, 10, and 15 mg, respectively. Overall, 113 subjects received vicriviroc at randomization or after virologic failure, and 52 (46%) achieved HIV-1 RNA <50 copies per milliliter within 24 weeks. Through 3 years, 49% of those achieving suppression did not experience confirmed viral rebound. Dual or mixed-tropic HIV-1 was detected in 33 (29%). Vicriviroc resistance (progressive decrease in maximal percentage inhibition on phenotypic testing) was detected in 6 subjects. Nine subjects discontinued vicriviroc due to adverse events. Vicriviroc seems safe and demonstrates sustained virologic suppression through 3 years of follow-up. Further trials of vicriviroc will establish its clinical utility for the treatment of HIV-1 infection.

  17. Three-Year Safety and Efficacy of Vicriviroc, a CCR5 Antagonist, in HIV-1-Infected, Treatment-Experienced Patients

    PubMed Central

    Wilkin, Timothy J.; Su, Zhaohui; Krambrink, Amy; Long, Jianmin; Greaves, Wayne; Gross, Robert; Hughes, Michael D.; Flexner, Charles; Skolnik, Paul R.; Coakley, Eoin; Godfrey, Catherine; Hirsch, Martin; Kuritzkes, Daniel R.; Gulick, Roy M.

    2010-01-01

    Background Vicriviroc, an investigational CCR5 antagonist, demonstrated short-term safety and antiretroviral activity. Methods Phase 2, double-blind, randomized study of vicriviroc in treatment-experienced subjects with CCR5-using HIV-1. Vicriviroc (5, 10 or 15 mg) or placebo was added to a failing regimen with optimization of background antiretroviral medications at day 14. Subjects experiencing virologic failure and subjects completing 48 weeks were offered open-label vicriviroc. Results 118 subjects were randomized. Virologic failure (<1 log10 decline in HIV-1 RNA ≥16 weeks post-randomization) occurred by week 48 in 24/28 (86%), 12/30 (40%), 8/30 (27%), 10/30 (33%) of subjects randomized to placebo, 5, 10 and 15 mg respectively. Overall, 113 subjects received vicriviroc at randomization or after virologic failure, and 52 (46%) achieved HIV-1 RNA <50 copies/mL within 24 weeks. Through 3 years, 49% of those achieving suppression did not experience confirmed viral rebound. Dual or mixed-tropic HIV-1 was detected in 33 (29%). Vicriviroc resistance (progressive decrease in maximal percentage inhibition on phenotypic testing) was detected in 6 subjects. Nine subjects discontinued vicriviroc due to adverse events. Conclusions Vicriviroc appears safe and demonstrates sustained virologic suppression through 3 years of follow-up. Further trials of vicriviroc will establish its clinical utility for the treatment of HIV-1 infection. PMID:20672447

  18. Syphilis Infection Differentially Regulates the Phenotype and Function of γδ T Cells in HIV-1-Infected Patients Depends on the HIV-1 Disease Stage

    PubMed Central

    Li, Zhen; Lu, Xiaofan; Hu, Zhiliang; Luo, Zhenwu; Jiang, Wei; Wu, Hao; Gao, Yanqing; Yan, Junling; Zhang, Qiuyue; Song, Aixin; Huang, Xiaojie; Mou, Danlei; Su, Bin; Zhang, Tong

    2017-01-01

    A rapidly escalating outbreak of syphilis infection has been affected men who have sex with men, particularly those with HIV-1 infection. γδ T cells are unconventional immune cells with two main subsets, Vδ1 T cells and Vδ2 T cells, which possess a combination of innate and adaptive immune features allowing them against HIV-1. However, whether syphilis infection affects the phenotype and function of γδ T cells in HIV-1-infected patients remains unclear, especially in acute HIV-1 infection (AHI). In this study, we enrolled 57 HIV-1-infected patients (24 with HIV-1 infection only and 33 coinfected with syphilis) from an acute HIV-1-infected cohort in Beijing (PRIMO). A comprehensive analysis of γδ T-cell phenotype and function was performed by flow cytometry. We found syphilis coinfection could reverse the imbalance of Vδ1/Vδ2 ratio in AHI. Syphilis infection results in decreased γδ T-cell activation in AHI, but increased γδ T-cell activation in chronic HIV-1 infection (CHI). Moreover, patients with CHI had larger numbers of IL-17-producing γδ T cells than those with AHI, regardless of syphilis status. Thus, syphilis affected the γδ T-cell immune response differently in patients depending on the stages of HIV-1 disease. In addition, the percentage of IL-17-producing γδ T cells was positively correlated with the percentage of neutrophils. These results suggest that the γδ T-cell/IL-17/neutrophil axis is involved in HIV-1 pathogenesis and disease progression. Taken together, our observations provide new insight into the roles of γδ T cells in immunopathogenesis of syphilis and HIV-1 coinfection, particularly during AHI, and our findings may be helpful for the prevention of syphilis and other sexually transmitted infections and highlight the great significance on the remedy of patients coinfected with HIV-1. PMID:28871259

  19. Tolerability of central nervous system symptoms among HIV-1 infected efavirenz users: analysis of patient electronic medical record data.

    PubMed

    Rosenblatt, Lisa; Broder, Michael S; Bentley, Tanya G K; Chang, Eunice; Reddy, Sheila R; Papoyan, Elya; Myers, Joel

    2017-02-01

    Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor indicated for treatment of HIV-1 infection. Despite concern over EFV tolerability in clinical trials and practice, particularly related to central nervous system (CNS) adverse events, some observational studies have shown high rates of EFV continuation at one year and low rates of CNS-related EFV substitution. The objective of this study was to further examine the real-world rate of CNS-related EFV discontinuation in antiretroviral therapy naïve HIV-1 patients. This retrospective cohort study used a nationally representative electronic medical records database to identify HIV-1 patients ≥12 years old, treated with a 1st-line EFV-based regimen (single or combination antiretroviral tablet) from 1 January 2009 to 30 June 2013. Patients without prior record of EFV use during 6-month baseline (i.e., antiretroviral therapy naïve) were followed 12 months post-medication initiation. CNS-related EFV discontinuation was defined as evidence of a switch to a replacement antiretroviral coupled with record of a CNS symptom within 30 days prior, absent lab evidence of virologic failure. We identified 1742 1st-line EFV patients. Mean age was 48 years, 22.7% were female, and 8.1% had a prior report of CNS symptoms. The first year, overall discontinuation rate among new users of EFV was 16.2%. Ten percent of patients (n = 174) reported a CNS symptom and 1.1% (n = 19) discontinued EFV due to CNS symptoms: insomnia (n = 12), headache (n = 5), impaired concentration (n = 1), and somnolence (n = 1). The frequency of CNS symptoms was similar for patients who discontinued EFV compared to those who did not (10.3 vs. 9.9%; P = .86). Our study found that EFV discontinuation due to CNS symptoms was low, consistent with prior reports.

  20. Prevalence of multiple dideoxynucleoside analogue resistance (MddNR) in a multicenter cohort of HIV-1-infected Italian patients with virologic failure.

    PubMed

    Balotta, C; Violin, M; Monno, L; Bagnarelli, P; Riva, C; Facchi, G; Berlusconi, A; Lippi, M; Rusconi, S; Clementi, M; Galli, M; Angarano, G; Moroni, M

    2000-07-01

    We evaluated the prevalence of both Q151M and 6-bp insert at position 69 of RT region responsible for multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 variants in 177 patients who failed to respond to combination therapy. Patients had received protease inhibitors (PI) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs) after a long-term experience with nucleoside reverse transcriptase inhibitors (NRTIs) (including zidovudine monotherapy). Two of 177 patients (1.1%) showed the specific complex of Q151M mutation, while 4 (2.3%) had the 69 6-bp insert. Mutations that belong to the 151 set in the absence of the pivotal Q151M substitution were detected in as many as 3.9% of the patients. One patient exhibited a 69S [VG] insert that has not been previously phenotypically characterized. This HIV-1 isolate had high levels of resistance to all NRTIs except stavudine. MddNR is an emerging problem after sequential therapy with this class of compounds among HIV-1-infected patients. Either didanosine (ddI) or zidovudine (ZDV) monotherapy allowed the emergence of MddNR variants containing Q151M complex. Monotherapy with ZDV and ddI or subsequent treatments with various NRTI combinations were the common background in the patients with the 69 insert. The overall prevalence of MddNR (3.4%) in Italy is comparable with that observed in several other European countries (3.4%-6.5%). These data suggest that patients failed by NRTI regimens should be analyzed for the presence of both patterns of MddNR.

  1. Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1-infected patients treated with two nucleoside reverse transcriptase inhibitors.

    PubMed

    Galli, Massimo; Ridolfo, Anna Lisa; Adorni, Fulvio; Gervasoni, Cristina; Ravasio, Laura; Corsico, Laura; Gianelli, Erika; Piazza, Manuela; Vaccarezza, Mauro; d'Arminio Monforte, Antonella; Moroni, Mauro

    2002-01-01

    Cross-sectional and retrospective surveys suggest that nucleoside reverse transcriptase inhibitors (NRTIs) contribute to the metabolic and morphologic alterations observed in patients on antiretroviral therapy (ART). To assess the risk of developing body habitus changes (BHCs) and metabolic abnormalities in protease inhibitor (PI)-naive HIV-1-infected patients treated with two NRTIs, and the risk associated with each of these drugs. Prospective cohort study. The BHCs occurring in 335 patients treated with two NRTIs were evaluated every 3 months. The laboratory tests included determination of CD4 cell counts and the measurement of HIV RNA, serum glucose, cholesterol, and triglyceride levels. Cox proportional hazard models were used to describe the factors associated with the development of BHCs. During a median exposure of 747.5 days, 46 patients (13.7%) developed BHCs: nine fat accumulation alone, 12 fat loss alone, and 25 combined fat loss and accumulation in different body regions. Fat loss alone occurred after a significantly longer median duration of treatment than the other two forms (p =.004). The risk of developing any BHC was significantly higher in female patients (p <.0001). Fat loss was the prevalent alteration in males. Hypertriglyceridemia was observed in 76 patients (22.7%), hypercholesterolemia in 35 (10.5%), and hyperglycemia in 48 (14.3%). The adjusted risk of developing hypertriglyceridemia was higher in the stavudine-treated patients (p =.04) and in those who had previously received ART (p =.02). The only independent factor associated with the development of hypercholesterolemia was to be ART experienced at baseline (p =.02), whereas age was associated with the development of hyperglycemia (p =.0096). Treatment with NRTIs may be responsible for the same morphologic alterations as those observed in patients treated with PIs. Moreover, altered triglyceride levels are also frequently observed. The different timing of presentation and gender

  2. Simeprevir plus sofosbuvir in patients with chronic hepatitis C virus genotype 1 infection and cirrhosis: A phase 3 study (OPTIMIST‐2)

    PubMed Central

    Matusow, Gary; DeJesus, Edwin; Yoshida, Eric M.; Felizarta, Franco; Ghalib, Reem; Godofsky, Eliot; Herring, Robert W.; Poleynard, Gary; Sheikh, Aasim; Tobias, Hillel; Kugelmas, Marcelo; Kalmeijer, Ronald; Peeters, Monika; Lenz, Oliver; Fevery, Bart; De La Rosa, Guy; Scott, Jane; Sinha, Rekha; Witek, James

    2016-01-01

    Hepatitis C virus (HCV)–infected patients with cirrhosis are historically a difficult‐to‐treat population and are at risk of hepatic decompensation. In the phase 2 COSMOS study that evaluated simeprevir (HCV NS3/4A protease inhibitor) + sofosbuvir (HCV nucleotide analogue NS5B polymerase inhibitor) ± ribavirin for 12 or 24 weeks in HCV genotype (GT)1–infected patients, high rates of sustained virologic response 12 weeks after planned end of treatment (SVR12) were achieved, including in patients with cirrhosis (METAVIR score F4). This phase 3, open‐label, single‐arm study (OPTIMIST‐2 [NCT02114151]) evaluated the efficacy and safety of 12 weeks of simeprevir + sofosbuvir in HCV GT1–infected treatment‐naive or treatment‐experienced patients with cirrhosis. Patients (aged 18‐70 years) with chronic HCV GT1 infection and documented presence of cirrhosis received oral simeprevir 150 mg once daily + sofosbuvir 400 mg once daily for 12 weeks. The primary efficacy endpoint of the study was the proportion of patients achieving SVR12 versus a composite historical control (SVR12 rate of 70%). Safety and patient‐reported outcomes were assessed. Overall, 103 patients received treatment. SVR12 with simeprevir + sofosbuvir (83%, 95% confidence interval 76%‐91%) met the primary objective of superiority versus the historical control (70%). SVR12 rates for treatment‐naive and treatment‐experienced patients were 88% (44/50) and 79% (42/53), respectively. Adverse events occurred in 72 (70%) patients, with most (64%) being grade 1 or 2. Serious adverse events (none considered related to study treatment) occurred in five (5%) patients, and three (3%) patients discontinued all study treatment due to adverse events. Patient‐reported outcomes improved from baseline to follow‐up week 12. Conclusion: Simeprevir + sofosbuvir for 12 weeks achieved superiority in SVR12 rates versus the historical control in treatment‐naive and treatment‐experienced HCV GT1

  3. Quantification of hepatitis C virus (HCV) RNA in a multicenter study: implications for management of HCV genotype 1-infected patients.

    PubMed

    Pisani, Giulio; Cristiano, Karen; Marino, Francesco; Luciani, Francesca; Bisso, Guillermo M; Mele, Claudio; Adriani, Daniela; Gentili, Giuliano; Wirz, Maria

    2009-09-01

    Assessment of the viral load in hepatitis C virus (HCV) genotype 1-infected patients is critical before, during, and after antiviral therapy. In patients achieving a rapid virological response at week 4 of treatment, the viral load at the baseline is considered a predictive criterion of a sustained virological response 24 weeks after the discontinuation of treatment. A >or=2-log(10) drop in the viral load at week 12 of treatment (early virological response) triggers the continuation of therapy. We organized a multicenter study (MS) for diagnostic laboratories involved in the quantification of HCV RNA. Commercial assays, including two based on real-time reverse transcription-PCR (TaqMan system), and in-house methods, were used by the 61 participants. The overall reproducibility of the commercial quantitative nucleic acid amplification techniques (qNAT) was acceptable. As the intermethod variability among commercial qNAT for HCV RNA was still present, the manufacturers of these test kits should join efforts to harmonize the means of quantification of HCV RNA. This study also shows that caution should be exercised when the baseline viral load is evaluated and when the 2-log(10) reduction after 12 weeks of therapy is interpreted. Finally, this MS confirms the higher sensitivity of the commercial qNAT based on the TaqMan system, making them the elective assays for the monitoring of therapy.

  4. Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies

    PubMed Central

    2012-01-01

    Objective To estimate the prognosis over 5 years of HIV-1-infected, treatment-naive patients starting HAART, taking into account the immunological and virological response to therapy. Design A collaborative analysis of data from 12 cohorts in Europe and north America on 20 379 adults who started HAART between 1995 and 2003. Methods Parametric survival models were used to predict the cumulative incidence at 5 years of a new AIDS-defining event or death, and death alone, first from the start of HAART and second from 6 months after the start of HAART. Data were analysed by intention-to-continue-treatment, ignoring treatment changes and interruptions. Results During 61 798 person-years of follow-up, 1005 patients died and an additional 1303 developed AIDS. A total of 10 046 (49%) patients started HAART either with a CD4 cell count of less than 200 cells/μl or with a diagnosis of AIDS. The 5-year risk of AIDS or death (death alone) from the start of HAART ranged from 5.6 to 77% (1.8–65%), depending on age, CD4 cell count, HIV-1-RNA level, clinical stage, and history of injection drug use. From 6 months the corresponding figures were 4.1–99% for AIDS or death and 1.3–96% for death alone. Conclusion On the basis of data collected routinely in HIV care, prognostic models with high discriminatory power over 5 years were developed for patients starting HAART in industrialized countries. A risk calculator that produces estimates for progression rates at years 1 to 5 after starting HAART is available from www.art-cohort-collaboration.org. PMID:17502729

  5. Distribution of HIV-1 Infection in Different T Lymphocyte Subsets: Antiretroviral Therapy-Naïve vs. Experienced Patients

    PubMed Central

    Perez, Raul; Gibson, Sonia; Lopez, Pablo; Koenig, Ellen; De Castro, Marisol

    2011-01-01

    Abstract Memory CD4 T cells are the primary targets of HIV-1 infection, which then subsequently spreads to other T lymphocyte subsets. Antiretroviral therapy (ART) alters the pattern of HIV-1 distribution. Blood samples were collected from ART-naïve or -experienced HIV-1 patients, and the memory and naïve subsets of CD4+ and CD8+ T lymphocytes, respectively, were isolated by cell sorting. DNA was extracted and the HIV-1 env C2/V3 region PCR amplified. Amplicons were cloned and sequenced, and genetic relatedness among different HIV-1 compartments was determined by the phylogenetic analysis of clonal sequences. The viral V3 sequence of HIV-1 in each compartment was analyzed by using webPSSM to determine CCR5 or CXCR4 coreceptor binding property of the virus. The direction of viral migration among involved compartments was determined by using the MacClade program. In ART-naïve patients, HIV-1 was generally confined to the memory CD4 T (mT4) cell compartment, even though in a few cases, naïve CD4 T (nT4) cells were also infected. When this occurred, the HIV-1 gene migrated from nT4 to mT4. In contrast, HIV-1 was detected in nT4 and mT4 as well as in the memory CD8 T (mT8) compartments of ART-experienced patients. However, no clear pattern of directional HIV-1 gene flow among the compartments could be determined because of the small sample size. All HIV-1–infected T cell compartments housed the virus that used either CCR5 or CXCR4 as the coreceptor. PMID:21054214

  6. Correlates of severe disease in patients admitted with 2009 pandemic influenza A (H1N1) infection in Saurashtra region, India

    PubMed Central

    Chudasama, Rajesh K.; Verma, Pramod B.; Amin, Chikitsa D.; Gohel, Bharat; Savariya, Dinkar; Ninama, Rakesh

    2010-01-01

    Background: India reported its first case of 2009 pandemic influenza A (H1N1) virus infection in May 2009 and in Saurashtra region in August 2009. We describe the epidemiology and factors associated with severe and non-severe cases of 2009 influenza A (H1N1) infection reported in Saurashtra region. Materials and Methods: From September 2009 to February 2010, we observed 274 patients who were infected with 2009 influenza A (H1N1) virus and admitted in different hospitals in Rajkot city. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) testing was used to confirm infection. Factors associated with severe disease were determined by comparing with non-severe cases. Results: Out of 274 patients, 87 had severe disease (requiring intensive care or died) and 187 had non-severe diseases (admitted in wards and survived). The median age of severe disease patients was 30 years; the median time was 5 days from the onset of illness to diagnosis, and 4 days median time was reported for hospital stay. More than half of the patients (56.3%) were females, and 58.6% patients were residing in urban area (OR = 1.65, CI = 0.97–2.8), among severe disease patients. Significant association (P < 0.01) was reported among severe disease patients for delayed referral from general practitioner/physician after initial treatment. All patients received antiviral drug, but only 19.5% received the same within 2 days of illness. Presence of coexisting condition [odds ratio (OR) = 0.53, confidence interval (CI) = 0.31–0.90], mainly pregnancy (OR = 0.22, CI = 0.06–0.76), was strongly associated with severe disease. Conclusion: Delayed referral from general practitioner/physician, duration of antiviral treatment, and presence of coexisting condition (especially pregnancy) were responsible for intensive care or mortality in patients of severe influenza A (H1N1) illness. PMID:21253344

  7. Effectively nursing patients receiving aromatase inhibitor therapy.

    PubMed

    Wengström, Y

    2008-06-01

    Inhibiting estrogen production is a common means of preventing breast cancer recurrence. The aromatase inhibitors (AIs) are becoming the preferred treatment over tamoxifen as adjuvant therapy for postmenopausal women with hormone-sensitive early breast cancer. Like all adjuvant therapies, AIs have adverse events (AEs) associated with their use, many of which resemble symptoms common to menopause. Because of the greater efficacy of AIs in preventing breast cancer recurrence over tamoxifen, these AEs may be considered tolerable by many patients and often can be effectively managed and/or prevented. Educating patients about anticipated AEs may help them understand, accept, and cope with these AEs. This article reviews the AEs associated with different adjuvant AI treatments and highlights some strategies to manage them effectively. It also highlights the importance of patient education regarding AI therapy and involvement in treatment decisions, which may lead to better long-term adherence and ultimately to better outcomes.

  8. Predictors for trismus in patients receiving radiotherapy.

    PubMed

    van der Geer, S Joyce; Kamstra, Jolanda I; Roodenburg, Jan L N; van Leeuwen, Marianne; Reintsema, Harry; Langendijk, Johannes A; Dijkstra, Pieter U

    2016-11-01

    Trismus, a restricted mouth opening in head and neck cancer patients may be caused by tumor infiltration in masticatory muscles, radiation-induced fibrosis or scarring after surgery. It may impede oral functioning severely. The aims of our study were to determine: (1) the incidence of trismus at various time points; and (2) the patient, tumor, and treatment characteristics that predict the development of trismus after radiotherapy in head and neck cancer patients using a large database (n = 641). Maximal mouth opening was measured prior to and 6, 12, 18, 24, 36, and 48 months after radiotherapy. Patient, tumor, and treatment characteristics were analyzed as potential predictors for trismus using a multivariable logistic regression analysis. At six months after radiotherapy, 28.1% of the patients without trismus prior to radiotherapy developed trismus for the first time. At subsequent time points the incidence declined. Over a total period of 48 months after radiotherapy, the incidence of trismus was 3.6 per 10 person years at risk. Patients who had tumors located in the oral cavity, oropharynx or nasopharynx, and the salivary glands or ear, and who had a longer overall treatment time of radiotherapy, were more likely to develop trismus in the first six months after radiotherapy. Maximal mouth opening was a predictor for developing trismus at all time points. Incidence of trismus is 3.6 per 10 person years at risk. Tumor localization and overall treatment time of radiotherapy are predictors for developing trismus the first six months after radiotherapy. Maximal mouth opening is a significant predictor for developing trismus at all time points. Regular measurements of maximal mouth opening are needed to predict trismus.

  9. Music therapy for patients receiving spine surgery.

    PubMed

    Lin, Pi-Chu; Lin, Man-Ling; Huang, Li-Ching; Hsu, Hsiu-Chu; Lin, Chiong-Chu

    2011-04-01

    The aim of this study was to evaluate the effects of music therapy on anxiety, postoperative pain and physiological reactions to emotional and physical distress in patients undergoing spinal surgery. Surgery-related anxiety and pain are the greatest concern of surgical patients, especially for those undergoing major procedures. A quasi-experimental study design was conducted in a medical centre in Taiwan from April-July 2006. Sixty patients were recruited. The study group listened to selected music from the evening before surgery to the second day after surgery. The control group did not listen to music. Patients' levels of anxiety and pain were measured with visual analogue scales (VAS). Physiological measures, including heart rate, blood pressure and 24-hour urinalysis, were performed. The average age of the 60 patients was 62·18 (SD 18·76) years. The mean VAS score for degree of anxiety in the study group was 0·8-2·0, compared with 2·1-5·1 in the control group. The mean VAS score for degree of pain in the study group was 1·7-3·0, compared with 4·4-6·0 in the control group. The differences between the two groups in VAS scores for both anxiety (p = 0·018-0·001) and pain (p = 0·001) were statistically significant. One hour after surgery, the mean blood pressure was significantly lower in the study group than in the control group (p = 0·014), but no significant differences were found between the two groups in urine cortisol (p = 0·145-0·495), norepinephrine (p = 0·228-0·626) or epinephrine values (p = 0·074-0·619). Music therapy has some positive effects on levels of anxiety and pain in patients undergoing spinal surgery. Complementary music therapy can alleviate pain and anxiety in patients before and after spinal surgery. © 2011 Blackwell Publishing Ltd.

  10. Necrotizing dermatitis in patients receiving cancer chemotherapy.

    PubMed

    Dreizen, S; McCredie, K B; Bodey, G P; Keating, M J

    1987-03-01

    Necrotizing dermatitis in patients being treated with cancer chemotherapeutic agents can be of several types. Microbial causes can include a variety of bacteria and fungi, the most common being Pseudomonas aeruginosa. Gangrene from occlusive causes is not uncommon among cancer patients with coexisting atheromatous, thromboembolic, or obliterative vascular disease. Toxic gangrene is most commonly caused by extravasation of intravenously administered cytotoxic antineoplastic drugs but has also been associated with the use of coumarin congeners and the bite of the brown recluse spider. Pyoderma gangrenosum is an idiopathic condition that has been reported in association with myeloproliferative disorders. Finally, necrosis can be caused by the neoplasm itself, when its growth is so great that blood vessels are compressed and ischemia of the surrounding tissue results.

  11. [Peritonitis in pediatric patients receiving peritoneal dialysis].

    PubMed

    Jellouli, Manel; Ferjani, Meriem; Abidi, Kamel; Hammi, Yosra; Boutiba, Ilhem; Naija, Ouns; Zarrouk, Chokri; Ben Abdallah, Taieb; Gargah, Tahar

    2015-12-01

    Peritonitis on catheter of dialysis represents the most frequent complication of the peritoneal dialysis (PD) in the pediatric population. It remains a significant cause of morbidity and mortality. In this study, we investigated the risk factors for peritonitis in children. In this study, we retrospectively collected the records of 85 patients who were treated with PD within the past ten years in the service of pediatrics of the University Hospital Charles-Nicolle of Tunis. Peritonitis rate was 0.75 episode per patient-year. Notably, peritonitis caused by Gram-positive organisms were more common. Analysis of infection risk revealed three significant independent factors: the poor weight (P=0.0045), the non-automated PD (P=0.02) and the short delay from catheter insertion to starting PD (P=0.02). The early onset peritonitis was significantly associated with frequent peritonitis episodes (P=0.0008). The mean duration between the first and second episode of peritonitis was significantly shorter than between PD commencement and the first episode of peritonitis. We revealed a significant association between Gram-negative peritonitis and the presence of ureterostomy (0.018) and between Gram-positive peritonitis and the presence of exit-site and tunnel infections (0.02). Transition to permanent hemodialysis was needed in many children but no death occurred in patients with peritonitis. Considering the important incidence of peritonitis in our patients, it is imperative to establish a targeted primary prevention. Nutritional care must be provided to children to avoid poor weight. The automated dialysis has to be the modality of choice. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  12. Increased prevalence and severity of radiographic hand osteoarthritis in patients with HIV-1 infection associated with metabolic syndrome: data from the cross-sectional METAFIB-OA study.

    PubMed

    Tomi, Anne-Laurence; Sellam, Jérémie; Lacombe, Karine; Fellahi, Soraya; Sebire, Manuela; Rey-Jouvin, Caroline; Miquel, Anne; Bastard, Jean-Philippe; Maheu, Emmanuel; Haugen, Ida K; Felson, David T; Capeau, Jacqueline; Girard, Pierre-Marie; Berenbaum, Francis; Meynard, Jean-Luc

    2016-12-01

    To determine radiographic hand osteoarthritis (HOA) prevalence in patients with HIV-1 infection in comparison with the general population and to address whether metabolic syndrome (MetS) may increase the risk of HOA during HIV-1 infection. Patients with HIV-1 infection and MetS (International Diabetes Federation, IDF criteria) aged 45-65 years were matched by age and gender to HIV-1-infected subjects without MetS and underwent hand radiographs. Framingham OA cohort was used as general population cohort. Radiographic HOA was defined as Kellgren-Lawrence (KL) score ≥2 on more than one joint. Radiographic severity was assessed by global KL score and number of OA joints. HOA prevalence was compared with that found in the Framingham study, stratified by age and sex. Logistic and linear regression models were used to determine the risk factors of HOA in patients with HIV-1 infection. 301 patients (88% male, mean age 53.4±5.0 years) were included, 152 with MetS and 149 without it. Overall, HOA prevalence was 55.5% and was higher for those with MetS than those without it (64.5% vs 46.3%, p=0.002). When considering men within each age group, HOA frequency was greater in patients with HIV-1 infection than the general population (all ages: 55.8% vs 38.7%; p<0.0001), due to the subgroup with MetS (64.9%; p<0.0001), as well as the subgroup without MetS, although not significant (46.6%; p=0.09). Risk of HOA was increased with MetS (OR 2.23, 95% 95% CI 1.26% to 3.96%) and age (OR 1.18, 95% CI 1.12 to 1.25). HOA severity was greater for patients with MetS than those without. HOA was not associated with previous or current exposure to protease inhibitors or HIV infection-related markers. HOA frequency is greater in patients with HIV-1 infection, especially those with MetS, than the general population. NCT02353767. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Lipid metabolism and lipodystrophy in HIV-1-infected patients: the role played by nonnucleoside reverse transcriptase inhibitors.

    PubMed

    Sension, Michael; Deckx, Henri

    2015-01-01

    Dyslipidemia and lipodystrophy represent significant healthcare concerns in HIV-infected patients due to their association with diabetes mellitus and increased cardiovascular disease risk. Since the lipid effects of the nonnucleoside reverse transcriptase inhibitors are not well characterized, we systematically summarized the effects of nonnucleoside reverse transcriptase inhibitor treatment on dyslipidemia and lipodystrophy in HIV-1 infection. As with other classes of antiretroviral agents, the nonnucleoside reverse transcriptase inhibitors are associated with lipid changes, although individual agents exhibit differing effects on lipid profiles. Comparative trials have shown that the risk for hypertriglyceridemia is lower with efavirenz than with the use of ritonavir-boosted lopinavir, but there is a greater likelihood of hypercholesterolemia compared to ritonavir-boosted atazanavir. Data also suggest that efavirenz results in greater increases in plasma lipid levels than integrase inhibitors and CC-chemokine-receptor-5 antagonists. Lipid disturbances are less frequent with the newer nonnucleoside reverse transcriptase inhibitors than with efavirenz. However, in most cases, no change in the total:high-density lipoprotein-cholesterol ratio was seen between the efavirenz and comparator groups. Switching from efavirenz to etravirine or rilpivirine, or the integrase inhibitors raltegravir or elvitegravir, resulted in significant reductions in lipid levels. There appears to be minimal potential for efavirenz or rilpivirine to result in development of lipodystrophy. Overall, nonnucleoside reverse transcriptase inhibitors have a smaller impact on plasma lipids than ritonavir-boosted protease inhibitors, with the newer agents exhibiting more favorable lipid profiles than efavirenz. When considering antiretroviral regimens, awareness of the different lipid effect profiles of the third agent is important, without forgetting the critical contribution of the background

  14. Gastrointestinal tolerability and quality of life in antiretroviral-naive HIV-1-infected patients: data from the CASTLE study.

    PubMed

    Malan, Niel; Su, Jun; Mancini, Marco; Yang, Rong; Wirtz, Victoria; Absalon, Judith; McGrath, Donnie

    2010-06-01

    Most ritonavir-boosted protease inhibitor (PI)-based antiretroviral regimens offer comparable levels of virological efficacy. Thus, the tolerability of the regimen becomes a distinguishing factor with implications for patient quality of life (QoL), treatment adherence, and clinical outcome. This article describes results from the CASTLE study (comparing once-daily atazanavir/ritonavir [ATV/RTV] with twice-daily lopinavir/ritonavir [LPV/RTV], both in combination with fixed-dose tenofovir/emtricitabine, in treatment-naive HIV-infected patients) and an evaluation of the impact of gastrointestinal (GI) complications of treatment on patient QoL, as measured by the irritable bowel syndrome (IBS) QoL questionnaire (IBS-QoL). Changes in IBS-QoL from baseline over time (to week 24) were classified as: "Improvement" (> or =2-point positive change from baseline), "No change" (<2-point change), or "Worsening" (> or =2-point negative change). Data were collected on GI adverse events (AEs) and use of GI medications. Of the 599 patients with IBS-QoL-evaluable data through week 24, fewer patients in the ATV/RTV group than in the LPV/RTV group experienced grade 2-4 treatment-related GI AEs including diarrhea (3% versus 10%), nausea (5% versus 7%), and vomiting (<1% on both arms). Nearly three times as many patients receiving LPV/RTV used GI medications. ATV/RTV was associated with an increase in overall IBS-QoL scores and more patients receiving ATV/RTV than LPV/RTV experienced improvement in IBS-QoL through week 24. In contrast to LPV/RTV, ATV/RTV treatment was associated with earlier and more positive improvements in QoL scores across CD4 sub-groups. Differences in the health-related QoL profile between ATV/RTV and LPV/RTV may be important when selecting PI-based antiretroviral regimens.

  15. Predictors of adverse outcomes in HIV-1-infected children receiving combination antiretroviral treatment: results from a DREAM cohort in sub-Saharan Africa.

    PubMed

    Marazzi, Maria Cristina; De Luca, Simona; Palombi, Leonardo; Scarcella, Paola; Ciccacci, Fausto; Ceffa, Susanna; Nielsen-Saines, Karin; De Luca, Andrea; Mancinelli, Sandro; Gennaro, Elisabetta; Zimba, Ines; Liotta, Giuseppe; Buonomo, Ersilia

    2014-03-01

    HIV-infected children have less access to combination antiretroviral therapy as compared with adults in resource-limited settings. Growth faltering, loss to follow-up (LTFU) and high mortality are frequently seen. A retrospective cohort study was performed with parameters extracted from the Drug Resource Enhancement against AIDS and Malnutrition database for HIV-infected, antiretroviral naïve children under 15 years presenting for care at 17 Drug Resource Enhancement against AIDS and Malnutrition centers in Mozambique, Malawi and Guinea between January 2005 to December 2008. Predictors of time-to-death, time-to-LTFU and persistence of malnutrition by Cox's regression and Kaplan-Meier were determined. 2215 children presented to care with 1343 (61%) being ≤ 5 years. At baseline, stunting and malnutrition occurred in 40% and 25%, respectively; 75% of 2149 children had CD4 cell percentages less than 20; median HIV RNA, log10 cp/mL, was 4.97 in 1927 patients. Over time 238 children died (10.7%; 2.7% person-years [PY]) 63 were LTFU (2.8%; 0.7% PY). By multivariate analysis, mortality was associated with virus load (hazards ratio: 1.19; confidence interval: 1.01-1.402, P = 0.038) and reduced weight-for-age Z scores (hazards ratio: 0.590; confidence interval: 0.53-0.66, P < 0.001). LTFU was associated with low weight-for-height Z scores (hazards ratio: 0.71; confidence interval: 0.51-0.97, P = 0.031). At 12 months after combination antiretroviral therapy, anthropometric parameters significantly improved in 1226 children (P < 0.001); virus load declined to <400 copies/mL in over 60%. Despite advanced HIV disease, children initiating combination antiretroviral therapy had mortality rates of 2.7% p/PY with overall attrition rates of 11.7% p/100 PY, with significant reversal of negative anthropometric markers, and improvement of immunological and virological parameters in children with 12 months of follow-up.

  16. Current perspectives on dental patients receiving coumarin anticoagulant therapy.

    PubMed

    Herman, W W; Konzelman, J L; Sutley, S H

    1997-03-01

    Despite approximately 40 years of experience with oral anticoagulant drugs, controversy still exists about the safety of dental treatment in a patient receiving this therapy. The authors review the topic in depth and offer detailed recommendations for the dental management of patients receiving coumarin anticoagulant therapy.

  17. Randomized controlled trial of Hepatitis B virus vaccine in HIV-1-infected patients comparing two different doses

    PubMed Central

    Cornejo-Juárez, Patricia; Volkow-Fernández, Patricia; Escobedo-López, Kenia; Vilar-Compte, Diana; Ruiz-Palacios, Guillermo; Soto-Ramírez, Luis Enrique

    2006-01-01

    Background Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is not infrequent as both share same route of exposure. The risk of developing chronic hepatitis B virus is 6%, in general population but can reach 10–20% in HBV/HIV co-infected patients. When compared to general population, the response rate to HBV vaccine in HIV-infected patients is diminished, so previous studies have tried to improve this response using variety of schedules, doses and co-administration of immunomodulators. The purpose of this study was to evaluate two doses of recombinant HBV vaccine (10 or 40 μg), IM at 0, 1 and 6 months. Vaccination response was measured 30–50 days after last dose; titers of >9.9 IU/L were considered positive. Results Seventy-nine patients were included, 48 patients (60.7%) serconverted. Thirty-nine patients (49.3%) received 10 μg vaccine dose, 24 patients (61.5%) seroconverted. Forty patients (50.7%) received 40 μg vaccine dose, 24 (60%) seroconverted. There were no differences between two doses. A statistically significant higher seroconversion rate was found for patients with CD4 cell counts at vaccination ≥ 200 cel/mm3 (33 of 38 patients, 86.8%), compared with those with CD4 < 200 cel/mm3 (15 of 41, 36.6%), [OR 11.44, 95% IC 3.67–35.59, p = 0.003], there were no differences between two vaccine doses. Using the logistic regression model, CD4 count <200 cel/mm3 were significantly associated with non serologic response (p = 0.003). None other variables such as gender, age, risk exposure for HIV, viral load, type or duration of HAART or AIDS-defining illness, were asociated with seroconversion. Conclusion In this study, an increase dose of HBV vaccine did not show to increase the rate of response in HIV infected subjects. The only significant findings associated to the response rate was that a CD4 count ≥ 200 cel/mm3, we suggest this threshold at which HIV patients should be vaccinated. PMID:16600028

  18. Characteristics of Multidrug Resistant Shigella and Vibrio cholerae O1 Infections in Patients Treated at an Urban and a Rural Hospital in Bangladesh

    PubMed Central

    Das, Sumon Kumar; Klontz, Erik H.; Azmi, Ishrat J.; Ud-Din, Abu I. M. S.; Chisti, Mohammod Jobayer; Afrad, Mokibul Hassan; Malek, Mohammad Abdul; Ahmed, Shahnawaz; Das, Jui; Talukder, Kaisar Ali; Salam, Mohammed Abdus; Bardhan, Pradip Kumar; Faruque, Abu Syed Golam; Klontz, Karl C.

    2013-01-01

    We determined the frequency of multidrug resistant (MDR) infections with Shigella spp. and Vibrio cholerae O1 at an urban (Dhaka) and rural (Matlab) hospital in Bangladesh. We also compared sociodemographic and clinical features of patients with MDR infections to those with antibiotic-susceptible infections at both sites. Analyses were conducted using surveillance data from the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), for the years 2000–2012. Compared to patients with antibiotic-susceptible for Shigella infections, those in Dhaka with MDR shigellosis were more likely to experience diarrhea for >24 hours, while, in Matlab, they were more likely to stay inhospital >24 hours. For MDR shigellosis, Dhaka patients were more likely than those in Matlab to have dehydration, stool frequency >10/day, and diarrheal duration >24 hours. Patients with MDR Vibrio cholerae O1 infections in Dhaka were more likely than those in Matlab to experience dehydration and stool frequency >10/day. Thus, patients with MDR shigellosis and Vibrio cholerae O1 infection exhibited features suggesting more severe illness than those with antibiotic-susceptible infections. Moreover, Dhaka patients with MDR shigellosis and Vibrio cholerae O1 infections exhibited features indicating more severe illness than patients in Matlab. PMID:24455398

  19. Twice-daily amprenavir 1200 mg versus amprenavir 600 mg/ritonavir 100 mg, in combination with at least 2 other antiretroviral drugs, in HIV-1-infected patients

    PubMed Central

    Nadler, Jeffrey P; Gathe, Joseph C; Pollard, Richard B; Richmond, Gary J; Liao, Qiming; Griffith, Sandy; Tracey Lancaster, C; Hernandez, Jaime E; Pappa, Keith A

    2003-01-01

    Background Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA <200 copies/mL at week 24 with APV 600/RTV minus APV1200 was ≥-0.12. Late in the conduct of the trial, patients not yet completing 24 weeks of therapy were given the option of continuing treatment for an additional 24-week period. Results 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA <200 copies/mL in 62% [73/118] vs 53% [20/38] of patients; intent-to-treat: observed analysis). In the APV600/RTV arm, significantly more patients achieved HIV-1 RNA <50 copies/mL (48% [57/118] vs 29% [11/38] with APV1200, P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1–4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA <200 copies/mL at week 24 and chose to continue study treatment maintained this level of virologic

  20. Disseminated Penicillium marneffei infection as an imported disease in HIV-1 infected patients. Description of two cases and a review of the literature.

    PubMed

    Kok, I; Veenstra, J; Rietra, P J; Dirks-Go, S; Blaauwgeers, J L; Weigel, H M

    1994-01-01

    Two cases of disseminated Penicillium marneffei infection, as an imported disease, in HIV-1-infected patients with a severe immunodeficiency are reported. These patients had a history of travel in Southeast Asia where P. marneffei is endemic. Fever, cough, malaise, hepatosplenomegaly, anaemia, skin lesions and mucosal ulcers are the main clinical characteristics. Differentiation from histoplasmosis and leishmaniasis might be difficult. Treatment with amphotericin B was successful. Anti-fungal maintenance therapy is most likely indicated.

  1. Comparison of hospitalized solid organ transplant recipients and nonimmunocompromised patients with pandemic H1N1 infection: a retrospective cohort study.

    PubMed

    Minnema, Brian J; Patel, Mehul; Rotstein, Coleman; Mazzulli, Tony; Hota, Susy; Cole, Edward H; Renner, Eberhard L; Ross, Heather J; Singer, Lianne G; Husain, Shahid

    2011-07-27

    Pandemic H1N1 influenza has been associated with a worldwide outbreak of febrile respiratory illness. Although impaired cell mediated immunity, such as that caused by transplant immunosuppression, has been identified as a risk factor for severe infection with this virus, the course of this infection has not been adequately characterized in solid organ transplant (SOT) recipients in comparison with nontransplanted controls. We report our experience with severe pH1N1 infection in transplant recipients and compare this group with nonimmunosuppressed patients. Data were retrospectively collected on all patients admitted to our institution with proven pH1N1 infection. Clinical characteristics, treatments, and outcomes were compared between SOT recipients and nonimmunocompromised controls. Seventeen SOT recipients and 49 controls were identified. The control group had higher baseline rates of asthma (P = 0.02) and smoking (P = 0.05) at baseline. No difference in clinical features of H1N1 infection was detected except for a greater prevalence of wheeze in the non-SOT group (P = 0.02). No statistical differences in outcomes could be detected between the groups. Several markers of severity, including use of high frequency oscillatory ventilation, extracorporeal membrane oxygenation, and death were slightly more frequent in the control group. SOT recipients admitted to hospital with pH1N1 infection did not have significantly more severe outcomes of their infection compared with their nonimmunocompromised counterparts, despite their immune suppressed status.

  2. Dolutegravir-based monotherapy or dual therapy maintains a high proportion of viral suppression even in highly experienced HIV-1-infected patients.

    PubMed

    Gubavu, Camelia; Prazuck, Thierry; Niang, Mohamadou; Buret, Jennifer; Mille, Catherine; Guinard, Jérôme; Avettand-Fènoël, Véronique; Hocqueloux, Laurent

    2016-04-01

    Dolutegravir is a powerful, well-tolerated integrase inhibitor with a high genetic barrier to resistance and may thus constitute the backbone of lightened regimens. This was a monocentric, retrospective study. HIV-1-infected patients receiving dolutegravir as monotherapy (mDGV) or dual therapy (dDGV) were systematically identified. The primary outcome was the proportion of patients who maintained undetectable (<50 copies/mL) plasma HIV RNA [plasma viral load (PVL)]. We identified 21 patients on mDGV (50 mg/day) and 31 on dDGV (50 or 100 mg/day, with atazanavir  ±  ritonavir, n = 12; rilpivirine, n = 11; maraviroc, n = 3; lamivudine, n = 3; darunavir/ritonavir, n = 1; or abacavir, n = 1). All of the patients were treatment experienced and 48% had experienced at least one virological failure. The baseline characteristics were as follows (for the mDGV/dDGV patients, respectively): 5%/29% had a history of AIDS; the median (IQR) highest PVL was 4.5 (4.3-5.5)/5.3 (4.7-5.6) log copies/mL; the median (IQR) nadir CD4+ count was 310 (280-468)/199 (134-281) cells/mm(3); 100% had undetectable PVL before the mDGV for a median (IQR) duration of 5.9 (3.5-9.9) years/81% had undetectable PVL before the dDGV for a median (IQR) duration of 3.7 (1.4-8.3) years; and the median (IQR) HIV DNA level was 2.7 (2.1-3.1)/2.9 (2.7-3) log copies/10(6) PBMCs. At the last follow-up visit, 100% and 97% of patients showed undetectable PVL following mDGV and dDGV, respectively [median (IQR) follow-up of 32 (29-45) and 50 (30-74) weeks, respectively]. In our experience, dolutegravir-based lightened regimens provided a high proportion of viral suppression, even in highly treatment-experienced patients. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

  3. Dolutegravir-based monotherapy or dual therapy maintains a high proportion of viral suppression even in highly experienced HIV-1-infected patients

    PubMed Central

    Gubavu, Camelia; Prazuck, Thierry; Niang, Mohamadou; Buret, Jennifer; Mille, Catherine; Guinard, Jérôme; Avettand-Fènoël, Véronique; Hocqueloux, Laurent

    2016-01-01

    Background Dolutegravir is a powerful, well-tolerated integrase inhibitor with a high genetic barrier to resistance and may thus constitute the backbone of lightened regimens. Methods This was a monocentric, retrospective study. HIV-1-infected patients receiving dolutegravir as monotherapy (mDGV) or dual therapy (dDGV) were systematically identified. The primary outcome was the proportion of patients who maintained undetectable (<50 copies/mL) plasma HIV RNA [plasma viral load (PVL)]. Results We identified 21 patients on mDGV (50 mg/day) and 31 on dDGV (50 or 100 mg/day, with atazanavir ± ritonavir, n = 12; rilpivirine, n = 11; maraviroc, n = 3; lamivudine, n = 3; darunavir/ritonavir, n = 1; or abacavir, n = 1). All of the patients were treatment experienced and 48% had experienced at least one virological failure. The baseline characteristics were as follows (for the mDGV/dDGV patients, respectively): 5%/29% had a history of AIDS; the median (IQR) highest PVL was 4.5 (4.3–5.5)/5.3 (4.7–5.6) log copies/mL; the median (IQR) nadir CD4+ count was 310 (280–468)/199 (134–281) cells/mm3; 100% had undetectable PVL before the mDGV for a median (IQR) duration of 5.9 (3.5–9.9) years/81% had undetectable PVL before the dDGV for a median (IQR) duration of 3.7 (1.4–8.3) years; and the median (IQR) HIV DNA level was 2.7 (2.1–3.1)/2.9 (2.7–3) log copies/106 PBMCs. At the last follow-up visit, 100% and 97% of patients showed undetectable PVL following mDGV and dDGV, respectively [median (IQR) follow-up of 32 (29–45) and 50 (30–74) weeks, respectively]. Conclusions In our experience, dolutegravir-based lightened regimens provided a high proportion of viral suppression, even in highly treatment-experienced patients. PMID:26712907

  4. [Factors associated with immunovirologic dissociation in HIV-1-infected patients under highly active antiretroviral therapy in the Ambulatory Treatment Center (ATC) in Dakar].

    PubMed

    Kà, Daye; Manga, Noël Magloire; Ngom-Guéye, Ndéye Fatou; Ndiaga, Diop; Diop, Moustapha; Cisse-Diallo, Viviane Marie Pierre; Diallo-Mbaye, Khardiata; Lakhe, Ndèye Aissatou; Fortès-Déguenonvo, Louise; Ndour, Cheikh Tidiane; Diop-Nyafouna, Sylvie Audrey; Seydi, Moussa

    2017-01-01

    The objective of this work is to evaluate the different factors associated with immunovirologic dissociation despite highly active and effective antiretroviral treatment. We conducted a retrospective, cohort, descriptive and analytical study of the medical records of HIV-1 infected patients having received at least 12 months of antiretroviral therapy, followed in the ATC cohort from 2001 to 2011 and with undetectable viral load in the last 6 months. During this 10-year study period, the prevalence of IVD was 19.3%. Female sex was predominant, with a sex ratio of 1.9. Immunovirologic dissociation was more frequent in male patients (29.7% vs 14.1%) with a statistically significant difference (p = 0,00006). The average age was 44 years ± 10 years. A history of tuberculosis was found in about a third of the cases (31.4%). Immunovirologic dissociation was significantly more frequent in patients with a history of tuberculosis (p = 0.00005). Most patients (68%) had AIDS at WHO clinical stages 3 or 4. Patients with immunovirologic dissociation were more often in WHO clinical stages 3 and 4 (p = 0.0001). More than half of the cases (56.2%) were found to be malnourished and immunovirologic dissociation was prevalent in malnourished patients (p=0.005). The mean CD4+ T lymphocytes counts was 86.7± 83 cells / mm(3). Immunovirologic dissociation was more frequent in patients with initial low CD4+ T lymphocyte counts and with a statistically significant difference (p = 0.00000). By multivariate analysis, only age greater than or equal to 43 years, CD4 initial counts < 100 c/mm(3) and male sex were significantly associated with this immunovirologic dissociation. Our study assessed the main factors associated with immunovirologic dissociation. Other studies of this nature would also merit consideration in order to highlight the impact of this partial immune response on the emergence of opportunistic infections or the implementation of a specific tritherapy for the sole purpose of

  5. Treatment of Immunocompromised, Critically Ill Patients with Influenza A H1N1 Infection with a Combination of Oseltamivir, Amantadine, and Zanamivir.

    PubMed

    Meijer, Wouter J; Kromdijk, Wiete; van den Broek, Marcel P H; Haas, Pieter-Jan A; Minnema, Monique C; Boucher, Charles A; de Lange, Dylan W; Wensing, Annemarie M J

    2015-01-01

    Immunocompromised patients are at increased risk of complications of influenza virus infection. We report on two critically ill patients on immunosuppressive medication with influenza pneumonia. In both patients, oseltamivir monotherapy did not result in clearance of the virus after 18 and five days, respectively. After adding zanamivir and amantadine to the treatment, PCRs on pharyngeal and/or plasma specimens turned negative in both patients after four and three days, respectively. We suggest, that in critically ill patients with influenza A H1N1 infection, treatment efficacy should be monitored closely and treatment with a combination of antiviral drugs should be considered.

  6. Treatment of Immunocompromised, Critically Ill Patients with Influenza A H1N1 Infection with a Combination of Oseltamivir, Amantadine, and Zanamivir

    PubMed Central

    Meijer, Wouter J.; Kromdijk, Wiete; van den Broek, Marcel P. H.; Haas, Pieter-Jan A.; Minnema, Monique C.; Boucher, Charles A.; de Lange, Dylan W.; Wensing, Annemarie M. J.

    2015-01-01

    Immunocompromised patients are at increased risk of complications of influenza virus infection. We report on two critically ill patients on immunosuppressive medication with influenza pneumonia. In both patients, oseltamivir monotherapy did not result in clearance of the virus after 18 and five days, respectively. After adding zanamivir and amantadine to the treatment, PCRs on pharyngeal and/or plasma specimens turned negative in both patients after four and three days, respectively. We suggest, that in critically ill patients with influenza A H1N1 infection, treatment efficacy should be monitored closely and treatment with a combination of antiviral drugs should be considered. PMID:26346659

  7. Transmitted Drug Resistance Among Antiretroviral-Naive Patients with Established HIV Type 1 Infection in Santo Domingo, Dominican Republic and Review of the Latin American and Caribbean Literature

    PubMed Central

    Taylor, Barbara S.; Rojas Fermín, Rita A.; Reyes, Emily Virginia; Vaughan, Catherine; José, Lina; Javier, Carmen; Franco Estévez, Ramona; Donastorg Cabral, Yeycy; Batista, Arelis; Lie, Yolanda; Coakley, Eoin; Hammer, Scott M.; Brudney, Karen

    2012-01-01

    Abstract Emergence of HIV resistance is a concerning consequence of global scale-up of antiretroviral therapy (ART). To date, there is no published information about HIV resistance from the Dominican Republic. The study's aim was to determine the prevalence of transmitted drug resistance (TDR) to reverse transcriptase and protease inhibitors in a sample of chronically HIV-1-infected patients in one clinic in Santo Domingo. The data are presented in the context of a review of the TDR literature from Latin America and the Caribbean. Genotype testing was successfully performed on 103 treatment-naive adults planning to initiate antiretroviral therapy; the World Health Organization (WHO) list of surveillance drug resistance mutations (SDRM) was used to determine the presence of TDR mutations. WHO SDRM were identified in eight patients (7.8%); none had received sdNVP. There were no significant differences in epidemiologic or clinical variables between those with or without WHO SDRM. The prevalence of WHO SDRM was 1.0% and 6.8% for nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. No WHO SDRMs for protease inhibitors were identified. Among 12 studies of TDR in the region with a sample size of at least 100 subjects, the reported prevalence of SDRM ranged from 2.8% to 8.1%. The most commonly identified SDRM was K103N. This information adds to our understanding of the epidemiology of TDR in the region and the possible role such mutations could play in undermining first-line treatment. Ongoing surveillance is clearly needed to better understand the TDR phenomenon in the Caribbean. PMID:21851324

  8. Older age does not influence CD4 cell recovery in HIV-1 infected patients receiving Highly Active Anti Retroviral Therapy

    PubMed Central

    Tumbarello, Mario; Rabagliati, Ricardo; de Gaetano Donati, Katleen; Bertagnolio, Silvia; Montuori, Eva; Tamburrini, Enrica; Tacconelli, Evelina; Cauda, Roberto

    2004-01-01

    Background Diagnosis of HIV infection is recently occurring with increasing frequency in middle-aged and in older individuals. As HAART became available, a minimal beneficial effect on immunological outcome in older in respect of younger subjects has been reported. In fact, both the intensity and the rapidity of the immunological response appeared to be reduced in elderly subjects. On the contrary, only few reports have indicated a similar immunological outcome both in older and younger HIV-positive subjects. Interestingly, older age did not seem to significantly affect the long-term virological outcome of HAART treated subjects. Methods To characterise epidemiological and clinical features of older HIV+ subjects, a prospective case-control study was performed: 120 subjects ≥ 50 and 476 between 20 and 35 years were initially compared. Subsequently, to better define the impact of HAART on their viro-immunological response, 81 older were compared with 162 younger subjects. Results At baseline cases presented significantly lower TCD4+ cell number and were more frequently affected by comorbid conditions. Under HAART a statistically significant increase in TCD4+ cell number was observed in cases and controls. At multivariate analysis, there was no statistically significant difference between cases and controls regarding viro-immunological response. Conclusions Although older subjects present a more severe HIV infection, they can achieve, under HAART, the same viro-immunological success as the younger individuals. PMID:15530169

  9. MicroRNA-29 family expression and its relation to antiviral immune response and viro-immunological markers in HIV-1-infected patients.

    PubMed

    Monteleone, Katia; Selvaggi, Carla; Cacciotti, Giulia; Falasca, Francesca; Mezzaroma, Ivano; D'Ettorre, Gabriella; Turriziani, Ombretta; Vullo, Vincenzo; Antonelli, Guido; Scagnolari, Carolina

    2015-02-12

    Several in vitro studies suggested the microRNA-29 (miRNA-29) family is involved in regulating HIV-1 and modulating the expression of interleukin (IL)-32, an anti-HIV-1 cytokine. To investigate the contribution of the miRNA-29 family to HIV-1 infection in vivo, we compared miRNA-29 expression in PBMC collected from 58 HIV-1-infected patients, naïve for antiretroviral therapy, and 21 gender- and age-matched HIV-1 seronegative healthy donors, using RT-Taqman assays. The relation between miRNA-29 levels and HIV-1 viro-immunological markers and the activation rate of antiviral immune response were also evaluated. In addition, we profiled miRNA-29 expression in CD4+ T lymphocytes and CD14+ monocytes collected from 5 antiretroviral treated HIV-1 infected patients. miRNA-29b levels were higher in HIV-1-infected patients than in the control group (p < 0.001). There were no correlations with either HIV-1 RNA levels or CD4+ T count, whereas a significant correlation was found between miRNA-29-a/c levels and integrated HIV-1 DNA (miRNA-29a: p = 0.009, r = -0.448; miRNA-29c: p = 0.029; r = -0.381). When the HIV-1-infected patients were grouped on the basis of their plasma HIV-1 RNA and CD4+ T cell count, we also found that patients expressing the lowest levels of miRNA-29c showed high viraemia, low CD4+ T cell count and high levels of integrated HIV-1 DNA. Moreover, miRNA-29b levels were correlated with those of IL-32nonα (p = 0.028; r = -0.298). Patients expressing higher levels of miRNA-29b showed lower levels of MxA, an interferon-stimulated gene, also induced by IL-32 (p = 0.006 r = -0.397). Lastly, we found that CD4+ T lymphocytes and CD14+ monocytes shared similar miRNA-29a/b/c expression patterns but the amount of miRNA-29a/b/c, IL-32 isoforms and MxA were highly variable in these two cellular subsets. The miRNA-29 family could influence the clinical progression of HIV-1 infection, the HIV-1 proviral load and the innate immune

  10. Exacerbation of microcytic anemia associated with cessation of anti-retroviral therapy in an HIV-1-infected patient with beta thalassemia.

    PubMed

    Furukawa, Yoshitaka; Hashiguchi, Teruto; Minami, Rumi; Yamamoto, Masahiro; Takashima, Hiroshi

    2014-06-01

    We report a patient with Japanese minor β thalassemia and HIV-1 infection. The patient showed prolonged anemia, which was originally attributed to chronic parvovirus B19 infection. Twelve years later, the patient presented with exacerbation of microcytic anemia following cessation of anti-retroviral therapy; the exacerbation resolved when anti-retroviral therapy was resumed. Sequencing of the β globin gene revealed heterozygosity for a four-nucleotides deletion at codon 41/42 and minor β thalassemia was confirmed. Because HIV-1-infected patients frequently show anemia due to nutritional deficiencies, opportunistic infections, AIDS-related malignancies, drug treatment and a direct effect of HIV-1 on the bone marrow, it is likely to overlook other causes of anemia. Thalassemia should be considered in the differential diagnosis of anemia even in HIV-1 infected patients, when microcytic anemia without iron deficiency is observed. Our case suggested that active HIV infection may have worsened β thalassemia, and early introduction of anti-retroviral therapy is beneficial for the recovery of anemia. Copyright © 2014 China Ordnance Society. Published by Elsevier Ltd. All rights reserved.

  11. Gastrointestinal symptoms and weight loss in cancer patients receiving chemotherapy.

    PubMed

    Sánchez-Lara, Karla; Ugalde-Morales, Emilio; Motola-Kuba, Daniel; Green, Dan

    2013-03-14

    Cancer patients receiving chemotherapy have a high risk of malnutrition secondary to the disease and treatment, and 40-80 % of cancer patients suffer from different degrees of malnutrition, depending on tumour subtype, location, staging and treatment strategy. Malnutrition in cancer patients affects the patient's overall condition, and it increases the number of complications, the adverse effects of chemotherapy and reduces the quality of life. The aim of the present study was to evaluate weight-loss prevalence depending on the tumour site and the gastrointestinal (GI) symptoms of oncology patients receiving chemotherapy. We included 191 cancer patients receiving chemotherapy. Files of all patients were reviewed to identify symptoms that might potentially influence weight loss. The nutritional status of all patients was also determined. The cancer sites in the patients were as follows: breast (31·9 %); non-colorectal GI (18·3 %); colorectal (10·4 %); lung (5·8 %); haematological (13·1 %); others (20·5 %). Of these patients, 58 % experienced some degree of weight loss, and its prevalence was higher among the non-colorectal GI and lung cancer patients. Common symptoms included nausea (59·6 %), anorexia (46 %) and constipation (31·9 %). A higher proportion of patients with ≥ 5 % weight loss experienced anorexia, nausea and vomiting (OR 9·5, 2·15 and 6·1, respectively). In conclusion, these results indicate that GI symptoms can influence weight loss in cancer patients, and they should be included in early nutritional evaluations.

  12. Clinico-Radiological Profile and Outcome of Novel H1N1-Infected Patients During 2009 to 2014 Pandemic at Tertiary Referral Hospital in Rajasthan.

    PubMed

    Maheshwari, Monika; Maheshwari, Sanjeev

    2015-05-01

    The 21st century Influenza A (H1N1) pandemic arrived during spring of 2009 and has posed a serious public health challenge world-wide. We describe the clinic-radiological profile and outcome of patients who were found H1N1 positive in Jawahar Lal Nehru Hospital, Ajmer of Rajasthan from 5th August 2009 to 31st May 2014. Primary objective was to study clinical and radiological profile of the patients admitted with confirmed H1N1 infection. Secondary objective was to observe the risk factors and associated comorbid conditions with complications and need of mechanical ventilation and / or death among H1N1-infected patients Hospitalized patient with laboratory-confirmed H1N1 flu by reverse transcriptase PCR during August 2009 to May 2014 in JLN Hospital, Ajmer, were included in this retrospective study. Data was collected from hospital isolation ward admission register. Statistical analysis was done by SPSS, version 16. Binary logistic regression was used to find out independent risk factors for morbidity. A total of 94 PCR-confirmed H1N1-infected patients were included in the study, of them 32 (34%) males and 62 (66%) females. Median age was 35 years and median duration of symptoms before hospitalization was 5 days. Common presenting symptoms include fever 83 (88%), cough 79 (84%), breathlessness 67 (71%), rhinnorrhoea/ common cold 25 (26.5%), throat pain 13 (13.8%), chest pain 5 (5.3%) and haemoptysis 4 (4.2%). Bilateral crepitations were audible in 86 (91.4%) and tachypnoea in 73 (78%) cases. Co-morbidities were seen in 75 (79.7%) patients. Ventilatory support was required in 57 (60.6%) patients. On presentation, chest x-ray showed pulmonary opacities in 72 (76.5%) patients. We observed no significant side effects of oseltamivir 150 mg twice day dose for 5-7 days. Forty-one (43.6%) patients were cured and discharged from hospital, 53 (56.3%) patients died. Development of ARDS, involvement of bilateral lower zones of lungs in chest skiagram, requirement of mechanical

  13. Enhanced mucosal reactions in AIDS patients receiving oropharyngeal irradiation

    SciTech Connect

    Watkins, E.B.; Findlay, P.; Gelmann, E.; Lane, H.C.; Zabell, A.

    1987-09-01

    The oropharynx and hypopharynx are common sites of involvement in AIDS patients with mucocutaneous Kaposi's sarcoma. The radiotherapist is often asked to intervene with these patients due to problems with pain, difficulty in swallowing, or impending airway obstruction. We have noted an unexpected decrease in normal tissue tolerance of the oropharyngeal mucosa to irradiation in AIDS patients treated in our department. Data on 12 patients with AIDS and Kaposi's sarcoma receiving oropharyngeal irradiation are presented here. Doses ranged from 1000 cGy to 1800 cGy delivered in 150-300 cGy fractions. Seven of eight patients receiving doses of 1200 cGy or more developed some degree of mucositis, four of these developed mucositis severe enough to require termination of treatment. All patients in this study received some form of systemic therapy during the course of their disease, but no influence on mucosal response to irradiation was noted. Four patients received total body skin electron treatments, but no effect on degree of mucositis was seen. Presence or absence of oral candidiasis was not an obvious factor in the radiation response of the oral mucosa in these patients. T4 counts were done on 9 of the 12 patients. Although the timing of the T4 counts was quite variable, no correlation with immune status and degree of mucositis was found. The degree of mucositis seen in these patients occurred at doses much lower than expected based on normal tissue tolerances seen in other patient populations receiving head and neck irradiations. We believe that the ability of the oral mucosa to repair radiation damage is somehow altered in patients with AIDS.

  14. Stress Encountered by Significant Others of Cancer Patients Receiving Chemotherapy.

    ERIC Educational Resources Information Center

    Hart, Kay

    1987-01-01

    Attempts to identify and describe perceived stress and coping responses of family and nonfamily significant others of cancer patients receiving chemotherapy. Significant others were asked to identify stressful events related to treatment factors, relationship factors, and perception of the patient's condition. Coping responses were categorized in…

  15. Outcomes of multiple myeloma patients receiving bortezomib, lenalidomide, and carfilzomib.

    PubMed

    Berenson, Ariana; Vardanyan, Suzie; David, Michael; Wang, James; Harutyunyan, Nika Manik; Gottlieb, Jillian; Halleluyan, Ran; Spektor, Tanya M; Udd, Kyle A; Eshaghian, Shahrooz; Nassir, Youram; Eades, Benjamin; Swift, Regina; Berenson, James R

    2017-03-01

    New classes of drugs including the proteasome inhibitors (PI) bortezomib and, more recently, carfilzomib and the immunomodulatory agent lenalidomide have shown improved outcomes for multiple myeloma (MM) patients during the past decade. However, most of the studies reporting outcomes for patients receiving these drugs have relied on older data sets derived from large institutions that included patients not receiving their treatment at those facilities and represented only those eligible for clinical trials or were from sites where treatment options were limited. We have analyzed data from 258 MM patients who have received treatment with at least one of three agents: bortezomib, carfilzomib, and lenalidomide in a single clinic specializing in MM with respect to their responses and other outcomes to treatment regimens including these agents. Response rates were similar between these three drugs when used for the first time and again during subsequent treatment regimens. As expected, the clinical benefit rates (CBRs) were better for patients receiving their first treatment when compared to their use in subsequent treatment regimens. The CBRs were similar during their 2nd, 3rd, and 4th treatments containing these agents. Many patients refractory to these agents showed responses to regimens containing these same drugs when used in different combinations. In addition, patients refractory to one PI often responded to the other PI. The results of this study demonstrate that novel agents can be used repeatedly in novel combinations with significant clinical benefit for patients with MM.

  16. Modulation of the proteome of peripheral blood mononuclear cells from HIV-1 infected patients by drugs of abuse

    PubMed Central

    Reynolds, Jessica L.; Mahajan, Supriya D.; Aalinkeel, Ravikunar; Nair, Bindukumar; Sykes, Donald E.; Agosto-Mujica, Arnadri; Hsiao, Chiu Bin; Schwartz, Stanley A.

    2010-01-01

    We used proteomic analyses to assess how drug abuse modulates immunologic responses to infections with the human immunodeficiency virus type 1 (HIV-1). Two dimensional (2D) difference gel electrophoresis was utilized to determine changes in the proteome of peripheral blood mononuclear cells (PBMC) isolated from HIV-1 positive donors that occurred after treatment with cocaine or methamphetamine. Both drugs differentially regulated the expression of several functional classes of proteins. We further isolated specific subpopulations of PBMC to determine which subpopulations were selectively affected by treatment with drugs of abuse. Monocytes, B cells and T cells were positively or negatively selected from PBMC isolated from HIV-1 positive donors. Our results demonstrate that cocaine and methamphetamine modulate gene expression primarily in monocytes and T cells, the primary targets of HIV-1 infection. Proteomic data were validated with quantitative, real-time PCR. These studies elucidate the molecular mechanisms underlying the effects of drugs of abuse on HIV-1 infections. Several functionally relevant classes of proteins were identified as potential mediators of HIV-1 pathogenesis and disease progression associated with drug abuse. PMID:19543960

  17. Osteonecrosis of the jaw in cancer patients receiving IV bisphosphonates.

    PubMed

    Van Poznak, Catherine; Estilo, Cherry

    2006-08-01

    Cases of osteonecrosis of the jaw (ONJ) have been reported with an increasing frequency over the past few years. ONJ is most often identified in patients with cancer who are receiving intravenous bisphosphonate therapy but it has also been diagnosed in patients receiving oral bisphosphonates for nonmalignant conditions. The condition involves exposed bone of the maxilla or mandible. Although it is often associated with a recent dental surgical procedure, spontaneous ONJ can also occur. Patients commonly present with symptoms. Through case reporting and clinical experience, there is a suggestion that the incidence of ONJ in patients with cancer receiving intravenous bisphosphonates ranges between 1% and 10%. Management of ONJ focuses on maximizing oral health, conservative actions with mouth rinses, antibiotics, and avoidance of unnecessary invasive dental procedures. The currently available data on ONJ are reviewed here.

  18. Vitamin D deficiency in patients receiving home parenteral nutrition.

    PubMed

    Thomson, Patti; Duerksen, Donald R

    2011-07-01

    In addition to its role in bone metabolism, vitamin D has important immunomodulatory and antineoplastic effects. Patients on home parenteral nutrition (HPN) receive most of their vitamin D from intravenous (IV) supplementation. Vitamin D deficiency is common in the general population, and the adequacy of vitamin D supplementation in HPN patients is unclear. The purpose of this study is to determine the vitamin D status of patients on HPN. Consecutive patients seen in a regional home nutrition program had their oral and IV vitamin D intakes determined. Plasma 25-hydroxyvitamin D levels were measured in all patients. Intake of calcium, magnesium, and phosphate were also determined. The mean 25-hydroxyvitamin D level in 22 patients receiving HPN for a mean of 33.5 months (range, 1-177) was 42 nmol/L. Vitamin D deficiency was present in 15 (68%) patients and vitamin D insufficiency in 6 (27%) patients. The mean dietary vitamin D intake was 79.5 IU per day, while the mean IV supplementation was 166 IU per day. In this study of a regional Canadian HPN program, there was a high prevalence of vitamin D deficiency/insufficiency affecting virtually all patients. All patients receiving HPN should be supplemented with vitamin D and have their 25-hydroxyvitamin D levels monitored. Further studies are required to determine optimal methods and dosing of vitamin D replacement using oral supplements or ultraviolet light therapy.

  19. RIG-I detects HIV-1 infection and mediates type I interferon response in human macrophages from patients with HIV-1-associated neurocognitive disorders

    PubMed Central

    Wang, M.Q.; Huang, Y.L.; Huang, J.; Zheng, J.L.; Qian, G.X.

    2016-01-01

    The aim of this study was to explore the precise role of retinoic acid-inducible gene-I (RIG-I) signaling in human immunodeficiency virus type 1 (HIV-1)-infected macrophages from patients with HIV-1-associated neurocognitive disorders (HAND). Postmortem brain tissues were collected from patients with HIV-1-associated dementia and were compared to samples collected from HIV serum-positive patients without dementia and HIV serum-negative patients. A human monocyte-derived macrophage (MDM) primary culture system was established to evaluate the expression of RIG-I in these samples. Knockdown of RIG-I pathways genes was employed and STAT1 expression and phosphorylation levels were examined to explore the molecular mechanisms of HAND. The expression of RIG-I in postmortem brain tissue from HAND patients was significantly higher than in patients who were HIV serum-positive without dementia or HIV serum-negative. Moreover, we demonstrated that HIV-1 infection could result in a significant increase in the level of RIG-I in human MDMs. Moreover, a correlation was found between the increase in RIG-I expression and STAT1 expression and phosphorylation. Accordingly, knockdown of RIG-I decreased the phosphorylation of STAT1 and downregulated interferon-related genes. These observations highlight the importance of RIG-I signaling in anti-HIV innate immunity in macrophages, which may be beneficial for the treatment of HIV and aid in the understanding of the neuropathogenesis of HAND. PMID:26535695

  20. Recurrent obstructive acute pyelonephritis: A rare form of Actinotignum (Actinobaculum) schaalii infection in a HIV-1 infected patient.

    PubMed

    Vallet, Anaïs; Noël, Nicolas; Bahi, Rachid; Teicher, Elina; Quertainmont, Yann; Delfraissy, Jean-François; Ferlicot, Sophie; Potron, Anaïs; Goujard, Cécile; Lambotte, Olivier

    2017-02-01

    Actinobaculum schaalii is a rarely reported, anaerobic, Gram-positive bacterium which role as uropathogen is emerging. We report here the case of a 47 year old HIV-1 infected woman presented with five recurrent episodes of obstructive pyelonephritis in the context of multiple renal stones. No bacteria was found until the fifth episode, during which prolonged urinary cultures as well as 16S rDNA sequencing allowed the diagnosis of A. schaalii infection. She had developed a life-threatening condition with severe renal failure. A right nephrectomy was performed and found that the intrarenal stones were attributed to the antiretroviral therapy. The renal parenchyma corresponded to an end-stage renal disease with chronic pyelonephritis without abcesses or granules. The situation improved after six months of amoxicillin therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. [Neurological complications in patients receiving solid organ transplants].

    PubMed

    Fernández-Ramos, J A; López-Laso, E; Ordóñez-Díaz, M D; Camino-León, R; Ibarra-de la Rosa, I; Frías-Pérez, M A; Gilbert-Pérez, J J; Pérez-Navero, J L

    2013-03-01

    Neurological complications (NC) are a significant cause of morbidity and mortality in paediatric patients receiving solid organ transplants. Our aim was to describe the experience of our hospital with NC in paediatric patients receiving heart, lung and liver transplants. A retrospective study was conducted on 140 paediatric patients who received a solid organ transplant during the period 2000-2011. A total of 23 paediatric solid organ transplant recipients (16.4% of cases), with a median age of 6 years, had NC. The symptoms were, in order of frequency: acute symptomatic seizures (12 patients); acute encephalopathy (11 patients); neuromuscular weakness (4 children), tremor (4 children), headache (2 children), neuropathic pain (2 children), and visual disturbances (2 children). The aetiologies of NC were: the neurotoxicity of the immunosuppressive drugs (12 patients), post-hypoxic-ischaemic encephalopathy (6 patients), infections (2 cases), mechanical compression of peripheral nerve during surgery (2 cases), and a metabolic complication (1 case). The five patients who met the criteria of posterior reversible encephalopathy syndrome had a favourable outcome. Seven patients died, four of them due to hypoxic-ischaemic encephalopathy. NC are common in paediatric patients receiving heart, liver, lung, and renal transplants, with acute symptomatic seizures and acute encephalopathy being the most common clinical signs. No differences were found in the NC with the different types of transplants. Neurotoxicity of the immunosuppressive drugs and hypoxic-ischaemic encephalopathy were the main causes of NC, having different management and outcomes. The prognosis was favourable in most of the patients, except for those who had moderate or severe post-hypoxic-ischaemic damage. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive Combined Antiretroviral Therapy.

    PubMed

    Liu, Bingfeng; Zou, Fan; Lu, Lijuan; Chen, Cancan; He, Dalian; Zhang, Xu; Tang, Xiaoping; Liu, Chao; Li, Linghua; Zhang, Hui

    2016-11-01

    antigen receptor, comprised of T cell activation domains and a broadly neutralizing antibody, VRC01, targeting HIV-1 to treat the infected cells. T cells expressing this construct exerted specific cytotoxic activity against wild-type HIV-1-infected cells, resulting in a dramatic reduction in viral rebound in vitro, and showed persistent effectiveness against reactivated latently infected T lymphocytes from HIV-1 patients receiving combined antiretroviral therapy. The methods used in this study constitute an improvement over existing CD4-based CAR-T technology and offer a promising approach to HIV-1 immunotherapy. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy☆,☆☆

    PubMed Central

    Gandhi, Rajesh T.; O'Neill, David; Bosch, Ronald J.; Chan, Ellen S.; Bucy, R. Pat; Shopis, Janet; Baglyos, Lynn; Adams, Elizabeth; Fox, Lawrence; Purdue, Lynette; Marshak, Ann; Flynn, Theresa; Masih, Reena; Schock, Barbara; Mildvan, Donna; Schlesinger, Sarah J.; Marovich, Mary A.; Bhardwaj, Nina; Jacobson, Jeffrey M.

    2010-01-01

    Targeting canarypox (CP)-HIV vaccine to dendritic cells (DCs) elicits anti-HIV-1 immune responses in vitro. We conducted a phase I/II clinical trial to evaluate whether adding DC to a CP-HIV vaccine improved virologic control during analytic treatment interruption (ATI) in HIV-1-infected subjects. Twenty-nine subjects on suppressive antiretroviral therapy were randomized to vaccination with autologous DCs infected with CP-HIV + keyhole limpet hemocyanin (KLH) (arm A, n = 14) or CP-HIV + KLH alone (arm B, n = 15). The mean viral load (VL) setpoint during ATI did not differ between subjects in arms A and B. A higher percentage of subjects in the DC group had a VL setpoint <5000 c/mL during ATI (4/13 or 31% in arm A compared with 0/13 in arm B, p = 0.096), but virologic control was transient. Subjects in arm A had a greater increase in KLH lymphoproliferative response than subjects in arm B; however, summed ELISPOT responses to HIV-1 antigens did not differ by treatment arm. We conclude that a DC-CP-HIV vaccine is well-tolerated in HIV-1-infected patients, but does not lower VL setpoint during ATI compared with CP-HIV alone. New methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed. PMID:19450647

  4. Hepatobiliary scintigraphy in patients receiving hepatic artery infusion chemotherapy

    SciTech Connect

    Housholder, D.F.; Hynes, H.E.; Dakhil, S.R.; Marymont, J.H. Jr.

    1984-01-01

    Two patients receiving hepatic artery infusion chemotherapy (HAIC) required cholecystectomy for both acute and chronic cholecystitis with cholelithiasis suggesting chemical cholecystitis. To evaluate the incidence of gall bladder dysfunction in patients receiving HAIC, the authors performed hepatobiliary scintigraphy using Tc-99m DISIDA or PIPIDA on eight patients receiving HAIC through an indwelling hepatic artery catheter and Infusaid (trademark) pump. In 7 of 8 patients, there was non-visualization of the gall bladder throughout the hepatobiliary study. In the eighth patient, the gall bladder visualized at 2 hr. One patient with non-visualization of the gall bladder at 4 hr developed acute symptoms requiring cholecystectomy which showed acute and chronic cholecystitis with cholethiasis. There was prominent sclerosis which was thought to be due to chemical cholecystitis as well as cholelithiasis. In all 10 patients, no evidence of cholecystitis had been observed during the surgical placement of the hepatic artery catheter and Infusaid pump. The hepatobiliary scintigraphic finding of gall bladder dysfunction in all eight patients studied is most likely due to chemical cholecystitis from HAIC. This series suggests that chemical cholecystitis is common during HAIC and can be identified by hepatobiliary scintigraphy. The authors consider elective cholecystectomy during the operative placement of the hepatic artery catheter and Infusaid pump.

  5. Intensification of Antiretroviral Therapy through Addition of Enfuvirtide in Naive HIV-1-Infected Patients with Severe Immunosuppression Does Not Improve Immunological Response: Results of a Randomized Multicenter Trial (ANRS 130 Apollo)

    PubMed Central

    Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick

    2013-01-01

    We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm3 or stage B/C disease with CD4 counts of <200/mm3. Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥200/mm3 at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm3, and the median HIV-1 RNA load was 5.4 log10 copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥200/mm3 at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression. PMID:23165467

  6. Intensification of antiretroviral therapy through addition of enfuvirtide in naive HIV-1-infected patients with severe immunosuppression does not improve immunological response: results of a randomized multicenter trial (ANRS 130 Apollo).

    PubMed

    Joly, Véronique; Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick

    2013-02-01

    We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm(3) or stage B/C disease with CD4 counts of <200/mm(3). Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥ 200/mm(3) at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm(3), and the median HIV-1 RNA load was 5.4 log(10) copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥ 200/mm(3) at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression.

  7. Assessing copper status in pediatric patients receiving parenteral nutrition.

    PubMed

    MacKay, Mark; Mulroy, Cecilia W; Street, Jennifer; Stewart, Charisse; Johnsen, Jake; Jackson, Daniel; Paul, Irasema

    2015-02-01

    Copper is a trace mineral essential for numerous physiological processes. The purpose of this article is to provide data on copper levels in pediatric patients receiving parenteral nutrition (PN) that are useful to guide supplementation in PN formulation. This is a retrospective review of hospitalized pediatric patients receiving PN supplemented and not supplemented with copper. In total, 751 supplemented pediatric patients and 90 pediatric patients not supplemented had serum copper levels measured. We assessed patient demographics, days on PN before copper level was drawn, serum copper levels, conjugated bilirubin levels, and C-reactive protein (CRP). The mean serum copper level was 80 mcg/dL at 20 days for supplemented patients and 64 mcg/dL at 14 days for the 90 nonsupplemented patients (P = .0002). In the supplemented patients, 50% of the levels were low and 45% were within the normal range. The remaining 5% of patients had high levels. In nonsupplemented patients, 71% were low and 29% within the normal range. There was no correlation between copper levels and conjugated bilirubin <2 mg/dL and >2 mg/dL (P = .3421). Copper levels correlated with CRP for CRP >4 mg/dL (P = .03). Pediatric patients receiving PN should be supplemented with copper to prevent deficiency. Serum copper levels should be assessed at 14 days. Assessment of copper status should not be determined by conjugated bilirubin levels. Serum copper levels may be elevated in patients with acute inflammation and may be falsely elevated when CRP is >4 mg/dL. © 2014 American Society for Parenteral and Enteral Nutrition.

  8. Prevalence of Human T-lymphotropic virus type 1 (HTLV-1) Infection in Patients with Hematologic Disorders and Non-Hematologic Malignancies in a Tertiary Referral Hospital.

    PubMed

    Jalaeikhoo, Hasan; Soleymani, Mosayeb; Rajaeinejad, Mohsen; Keyhani, Manoutchehr

    2017-04-01

    Human T-lymphotropic virus type 1 (HTLV-1) was the first retrovirus identified in human. The current evidence is quite scarce regarding the potential role of HTLV-1 in pathogenesis of hematologic disorders and non-hematologic malignancies. The aim of this study is to evaluate the prevalence of HTLV-1 infection in patients with hematologic disorders and non-hematologic malignancies. This cross-sectional study was conducted on 505 cases of definite diagnosis of hematologic disorders including malignancies as well as non-malignant disorders such as polycythemia and myelofibrosis and non-hematologic malignancies referred to the hematology and medical oncology ward at Army Hospital 501 from January 2015 to January 2016. A 3-mL blood specimen was collected from each patient and tested for the presence of anti-HTLV-1 antibodies using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using SPSS software package version 19 (IBM, New York, USA). Data are presented as mean ± SD if normally distributed and otherwise as median (range). Totally, 242 (48%) males and 263 (52%) females with a mean ± SD age of 52.09 ± 16.24 were enrolled in this study. In total, there were 9 (1.78%) cases positive for HTLV-1 infection including 4 males and 5 females. Seven out of 287 (2.4%) patients with hematologic disorders were infected by HTLV-1. In non-hematologic malignancies, 2 out of 211 cases were positive (0.9%). There was no HTLV-1 positive case in 7 patients with both hematologic and non-hematologic disorders. The difference in HTLV-1 infection prevalence between patients with hematologic disorders and non-hematologic malignancies was not statistically significant different (P = 0.31). There was no association between sex and transfusion history with HTLV-1 infection in this population (P = 0.9 and 0.7, respectively). Our study revealed that the prevalence of HTLV-1 in hematologic disorders is higher than the general population. Further larger prospective studies are

  9. New Horizon in Life: Experiences of Patients Receiving Chemotherapy

    PubMed Central

    Nasrabadi, Alireza Nikbakht; Mohammadpour, Ali; Fathi, Mohammad

    2016-01-01

    Introduction: The treatment quality of diseases can affect the patient's experience. Due to its different complications among cancer patients, the experience of chemotherapy is unique. The present study was conducted to explore the lived experience among cancer patients who had received chemotherapy. Methods: The study was conducted by a qualitative approach and a phenomenological method. In so doing, 12 cancer patients who had received chemotherapy were purposefully selected were interviewed using an in-depth method. After the required data were collected, they were analyzed by Tanner, Allen, Diekelmann method. Results: Analysis of the collected data indicated that the experience of chemotherapy appeared as “a new horizon in life” for the patients. Secondary themes of the new horizon in life included rebirth, understanding of life values, dependence, and need. Conclusion: According to the results of the study, it was concluded that in addition to taking into providing mental-spiritual support and reducing the complications of the treatment, nurses in chemotherapy wards should pay attention to the experiences of the patients receiving chemotherapy and enhance hope and positive attitude among them. PMID:26573050

  10. Patients With Brain Tumors: Who Receives Postacute Occupational Therapy Services?

    PubMed

    Chan, Vincy; Xiong, Chen; Colantonio, Angela

    2015-01-01

    Data on the utilization of occupational therapy among patients with brain tumors have been limited to those with malignant tumors and small samples of patients outside North America in specialized palliative care settings. We built on this research by examining the characteristics of patients with brain tumors who received postacute occupational therapy services in Ontario, Canada, using health care administrative data. Between fiscal years 2004-2005 and 2008-2009, 3,199 patients with brain tumors received occupational therapy services in the home care setting after hospital discharge; 12.4% had benign brain tumors, 78.2% had malignant brain tumors, and 9.4% had unspecified brain tumors. However, patients with benign brain tumors were older (mean age=63.3 yr), and a higher percentage were female (65.2%). More than 90% of patients received in-home occupational therapy services. Additional research is needed to examine the significance of these differences and to identify factors that influence access to occupational therapy services in the home care setting.

  11. Hepatitis C virus screening in patients with cancer receiving chemotherapy.

    PubMed

    Hwang, Jessica P; Suarez-Almazor, Maria E; Torres, Harrys A; Palla, Shana L; Huang, Donna S; Fisch, Michael J; Lok, Anna S F

    2014-05-01

    Reactivation of hepatitis C virus (HCV) replication can occur in patients receiving immunosuppressive therapy. We aimed to determine the prevalence and predictors of HCV screening at the onset of chemotherapy among patients with cancer. We conducted a retrospective cohort study of adults with cancer who were newly registered at MD Anderson Cancer Center from January 2004 to April 2011 and received chemotherapy. The primary study outcome was HCV antibody (anti-HCV) screening at chemotherapy onset. We calculated screening prevalence and predictors by comparing characteristics of screened and unscreened patients using multivariable logistic regression. A total of 141,877 new patients with cancer were registered at MD Anderson during the study period, of whom 16,773 (11.8%) received chemotherapy and met inclusion criteria. A total of 2,330 patients (13.9%) were screened for HCV, and 35 (1.5%) tested positive. Only 42% of patients with exposure-type HCV risk factors, such as HIV infection, injection drug use, hemodialysis, or hemophilia, were screened. Birth after 1965, Asian race, HCV risk factors, and anticipated rituximab therapy were significant predictors of HCV screening; black patients and patients with solid tumors were significantly less likely to be screened. The only significant predictor of a positive anti-HCV result was birth during 1945 to 1965. HCV screening rates were low, even among patients with risk factors, and the groups with the highest rates of screening did not match the groups with the highest rates of a positive test result. Misconceptions may exist about which patients should be screened for HCV infection. Copyright © 2014 by American Society of Clinical Oncology.

  12. Assessment of etravirine resistance in HIV-1-infected paediatric patients using population and deep sequencing: final results of the PIANO study.

    PubMed

    Tambuyzer, Lotke; Thys, Kim; Hoogstoel, Annemie; Nijs, Steven; Tomaka, Frank; Opsomer, Magda; De Meyer, Sandra; Vingerhoets, Johan

    2016-01-01

    We assessed etravirine resistance in treatment-experienced, HIV-1-infected children (n=41)/adolescents (n=60) who received twice-daily etravirine 5.2 mg/kg and a background regimen (boosted protease inhibitor plus nucleoside/nucleotide reverse transcriptase inhibitors, optional enfuvirtide/raltegravir) in a Phase II, open-label, multicentre trial (PIANO). In addition to phenotypes, viral genotypes were assessed by population and deep sequencing (PS and DS) in virological failures (VFs; baseline and end point) and responders (baseline). Minority resistance-associated mutations (RAMs) were defined as those with frequencies above 1% and not detected with PS. By week 48, 41/101 (40.6%) patients experienced VF; 17/41 (41.5%) VFs and 22/54 (40.8%) responders had ≥1 baseline etravirine RAM by PS, mainly A98G, K101E, V106I and G190A. Baseline minority etravirine RAMs (n) were detected in 8/40 VFs (V90I [2], A98G [1], L100I [1], V106I [1], E138G [1] and Y181C [2]) and 5/38 responders (V90I [3], A98G [1], V106I [1] and E138G [1]). The most frequent emerging non-nucleoside reverse transcriptase inhibitor RAMs detected by PS (≥3 VFs; n) were the etravirine RAMs Y181C (8), V90I (3), L100I (3) and E138A (3). In 15 of 29 (51.7%) VFs with baseline DS/PS and end point PS data, ≥1 emerging etravirine RAM was detected by PS, which was not detected at baseline by DS in most cases (12/15 [80.0%]). In 10/26 (38.5%) VFs with baseline/end point DS data, ≥1 additional emerging minority etravirine RAM was detected. Patterns of etravirine resistance in adults, adolescents and children experiencing VF are similar. The presence of minority etravirine RAMs at baseline was not consistently associated with treatment failure. ClinicalTrials.gov: NCT00665847.

  13. Intraepidermal nerve fibre density in cancer patients receiving adjuvant chemotherapy.

    PubMed

    Koskinen, Mika J; Kautio, Anna-Liisa; Haanpää, Maija L; Haapasalo, Hannu K; Kellokumpu-Lehtinen, Pirkko-L; Saarto, Tiina; Hietaharju, Aki J

    2011-12-01

    Chemotherapy-induced neuropathy is a common adverse event in patients receiving vinca alcaloids, platinum derivatives and taxanes. However, the underlying pathogenetic mechanisms have not been completely elucidated. We set up a prospective pilot study on skin biopsies in newly diagnosed cancer patients receiving neurotoxic chemotherapeutic agents as adjuvant treatment in order to study the occurrence of small-fibre pathology and its relationship to clinical symptoms. Skin biopsies from distal leg were performed in 12 patients before, during and after chemotherapy. Using light microscopy, the intraepidermal nerve fibre (IENF) density was determined from the skin biopsies by counting morphometrically the immunopositive nerves per epidermal area. Reduced IENF density was observed in eight patients at baseline. During the follow-up, the IENF density increased significantly in six patients and remained unchanged in two. In four patients, the IENF density was normal both at baseline and at the end of the follow-up period. Neuropathic symptoms were manifested in nine patients, but no association with the IENF count was found. During chemotherapy, results from patients revealed different evolutionary patterns of IENF density, but symptoms and IENF density were not related.

  14. Peritoneal mucormycosis in a patient receiving continuous ambulatory peritoneal dialysis.

    PubMed

    Polo, J R; Luño, J; Menarguez, C; Gallego, E; Robles, R; Hernandez, P

    1989-03-01

    A 48-year-old man receiving maintenance hemodialysis for 3 years and continuous ambulatory peritoneal dialysis for 1 year developed a clinical picture compatible with peritonitis. Three successive fluid cultures were negative, and only after filtration of a large volume of peritoneal fluid a fungus identified as a Rhizopus sp was isolated in cultures of the filtering devices. The same fungus was also isolated from the peritoneal catheter cuff. Intravenous amphotericin B was administered and both the abdominal and general conditions of the patient improved transiently. Twenty days after initiation of antifungal treatment, a clinical suspicion of intestinal perforation arose and an exploratory laparotomy was scheduled, but the patient died during the anesthetic induction. The patient never received deferoxamine; any conditions predisposing to mucormycosis, such as diabetes or immunosuppression, were also absent.

  15. A survey of patient views on receiving vascular outpatient letters.

    PubMed

    Brodie, T; Lewis, D R

    2010-01-01

    To assess the attitude of patients to receiving a copy of vascular outpatient clinic letters. 100 patients attending an outpatient vascular clinic at Christchurch Hospital were sent a copy of their outpatient letter along with a questionnaire. This gathered information on the content of the letter, their understanding of it, how useful they found it and whether they would want this practice to continue. The response rate was 68%. Ninety four percent of the responders believed receiving a copy of the letter was a good reinforcement of the information they received at the consultation. Ninety three percent of responders also found being copied into correspondence helpful and 96% understood the contents of the letters. Ninety seven percent wished to receive more letters in the future. These results suggest that vascular surgery patients both value and understand clinic letters, and that health professionals should consider adopting this practice into their vascular outpatient clinics. Copyright 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  16. Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy.

    PubMed

    Sánchez-Taltavull, Daniel; Vieiro, Arturo; Alarcón, Tomás

    2016-10-01

    HIV-1 infected patients are effectively treated with highly active anti-retroviral therapy (HAART). Whilst HAART is successful in keeping the disease at bay with average levels of viral load well below the detection threshold of standard clinical assays, it fails to completely eradicate the infection, which persists due to the emergence of a latent reservoir with a half-life time of years and is immune to HAART. This implies that life-long administration of HAART is, at the moment, necessary for HIV-1-infected patients, which is prone to drug resistance and cumulative side effects as well as imposing a considerable financial burden on developing countries, those more afflicted by HIV, and public health systems. The development of therapies which specifically aim at the removal of this latent reservoir has become a focus of much research. A proposal for such therapy consists of elevating the rate of activation of the latently infected cells: by transferring cells from the latently infected reservoir to the active infected compartment, more cells are exposed to the anti-retroviral drugs thus increasing their effectiveness. In this paper, we present a stochastic model of the dynamics of the HIV-1 infection and study the effect of the rate of latently infected cell activation on the average extinction time of the infection. By analysing the model by means of an asymptotic approximation using the semi-classical quasi steady state approximation (QSS), we ascertain that this therapy reduces the average life-time of the infection by many orders of magnitudes. We test the accuracy of our asymptotic results by means of direct simulation of the stochastic process using a hybrid multi-scale Monte Carlo scheme.

  17. Relation of activation-induced deaminase (AID) expression with antibody response to A(H1N1)pdm09 vaccination in HIV-1 infected patients.

    PubMed

    Cagigi, Alberto; Pensieroso, Simone; Ruffin, Nicolas; Sammicheli, Stefano; Thorstensson, Rigmor; Pan-Hammarström, Qiang; Hejdeman, Bo; Nilsson, Anna; Chiodi, Francesca

    2013-04-26

    The relevance of CD4+T-cells, viral load and age in the immunological response to influenza infection and vaccination in HIV-1 infected individuals has previously been pointed out. Our study aimed at assessing, in the setting of 2009 A(H1N1)pdm09 influenza vaccination, whether quantification of activation-induced deaminase (AID) expression in blood B-cells may provide additional indications for predicting antibody response to vaccination in HIV-1 infected patients with similar CD4+T-cell counts and age. Forty-seven healthy controls, 37 ART-treated and 17 treatment-naïve HIV-1 infected patients were enrolled in the study. Blood was collected prior to A(H1N1)pdm09 vaccination and at 1, 3 and 6 months after vaccination. Antibody titers to A(H1N1)pdm09 vaccine were measured by hemagglutination inhibition (HI) assay while the mRNA expression levels of AID were measured by quantitative real time PCR. Upon B-cell activation in vitro, AID increase correlated to antibody response to the A(H1N1)pdm09 vaccine at 1 month after vaccination in all individuals. In addition, the maximum expression levels of AID were significantly higher in those individuals who still carried protective levels of A(H1N1)pdm09 antibodies after 6 months from vaccination. No correlation was found between CD4+T-cell counts or age at vaccination or HIV-1 viral load and levels of A(H1N1)pdm09 antibodies. Assessing AID expression before vaccination may be an additional useful tool for defining a vaccination strategy in immune-compromised individuals at risk of immunization failure.

  18. A Metagenomic Analysis of Pandemic Influenza A (2009 H1N1) Infection in Patients from North America

    PubMed Central

    Greninger, Alexander L.; Chen, Eunice C.; Sittler, Taylor; Scheinerman, Alex; Roubinian, Nareg; Yu, Guixia; Kim, Edward; Pillai, Dylan R.; Guyard, Cyril; Mazzulli, Tony; Isa, Pavel; Arias, Carlos F.; Hackett, John; Schochetman, Gerald; Miller, Steve; Tang, Patrick; Chiu, Charles Y.

    2010-01-01

    Although metagenomics has been previously employed for pathogen discovery, its cost and complexity have prevented its use as a practical front-line diagnostic for unknown infectious diseases. Here we demonstrate the utility of two metagenomics-based strategies, a pan-viral microarray (Virochip) and deep sequencing, for the identification and characterization of 2009 pandemic H1N1 influenza A virus. Using nasopharyngeal swabs collected during the earliest stages of the pandemic in Mexico, Canada, and the United States (n = 17), the Virochip was able to detect a novel virus most closely related to swine influenza viruses without a priori information. Deep sequencing yielded reads corresponding to 2009 H1N1 influenza in each sample (percentage of aligned sequences corresponding to 2009 H1N1 ranging from 0.0011% to 10.9%), with up to 97% coverage of the influenza genome in one sample. Detection of 2009 H1N1 by deep sequencing was possible even at titers near the limits of detection for specific RT-PCR, and the percentage of sequence reads was linearly correlated with virus titer. Deep sequencing also provided insights into the upper respiratory microbiota and host gene expression in response to 2009 H1N1 infection. An unbiased analysis combining sequence data from all 17 outbreak samples revealed that 90% of the 2009 H1N1 genome could be assembled de novo without the use of any reference sequence, including assembly of several near full-length genomic segments. These results indicate that a streamlined metagenomics detection strategy can potentially replace the multiple conventional diagnostic tests required to investigate an outbreak of a novel pathogen, and provide a blueprint for comprehensive diagnosis of unexplained acute illnesses or outbreaks in clinical and public health settings. PMID:20976137

  19. [Cognitive plasticity in Alzheimer's disease patients receiving cognitive stimulation programs].

    PubMed

    Zamarrón Cassinello, Ma Dolores; Tárraga Mestre, Luis; Fernández-Ballesteros, Rocío

    2008-08-01

    The main purpose of this article is to examine whether cognitive plasticity increases after cognitive training in Alzheimer's disease patients. Twenty six patients participated in this study, all of them diagnosed with mild Alzheimer's disease, 17 of them received a cognitive training program during 6 months, and the other 9 were assigned to the control group. Participants were assigned to experimental or control conditions for clinical reasons. In order to assess cognitive plasticity, all patients were assessed before and after treatment with three subtests from the "Bateria de Evaluación de Potencial de Aprendizaje en Demencias" [Assessment Battery of Learning Potential in Dementia] (BEPAD). After treatment, Alzheimer's disease patients improved their performance in all the tasks assessing cognitive plasticity: viso-spatial memory, audio-verbal memory and verbal fluency. However, the cognitive plasticity scores of the patients in the control group decreased. In conclusion, this study showed that cognitive stimulation programs can improve cognitive functioning in mildly demented patients, and patients who do not receive any cognitive interventions may reduce their cognitive functioning.

  20. Immunological and Viral Features in Patients with Overactive Bladder Associated with Human T-Cell Lymphotropic Virus Type 1 Infection

    PubMed Central

    Santos, Silvane Braga; Oliveira, Paulo; Luna, Tania; Souza, Anselmo; Nascimento, Márcia; Siqueira, Isadora; Tanajura, Davi; Muniz, André Luiz; Glesby, Marshall J; Carvalho, Edgar M.

    2012-01-01

    The majority of patients infected with human T-cell lymphotropic virus-type 1 (HTLV-1) are considered carriers, but a high frequency of urinary symptoms of overactive bladder, common in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) have been documented in these patients. The aim of this study was to determine if immunological and viral factors that are seen in HAM/TSP are also observed in these patients. Participants were classified as HTLV-1 carriers (n=45), HTLV-1 patients suffering from overactive bladder (n=45) and HAM/TSP (n=45). Cells from HTLV-1 overactive bladder patients produced spontaneously more proinflammatory cytokines than carriers. TNF-α and IL-17 levels were similar in HAM/TSP and HTLV-1 overactive bladder patients. High proviral load was found in patients with overactive bladder and HAM/TSP and correlated with proinflammatory cytokines. In contrast with findings in patients with HAM/TSP, serum levels of Th1 chemokines were similar in HTLV-1 overactive bladder and carriers. Exogenous addition of regulatory cytokines decreased spontaneous IFN-γ production in cell cultures from HTLV-1 overactive bladder patients. The results show that HTLV-1 overactive bladder and HAM/TSP patients have in common some immunological features as well as similar proviral load profile. The data show that HTLV-1 overactive bladder patients are still able to down regulate their inflammatory immune response. In addition, these patients express levels of chemokines similar to carriers, which may explain why they have yet to develop the same degree of spinal cord damage as seen in patients with HAM/TSP. These patients present symptoms of overactive bladder, which may be an early sign of HAM/TSP. PMID:22997085

  1. ICU professionals' experiences of caring for conscious patients receiving MVT.

    PubMed

    Karlsson, Veronika; Bergbom, Ingegerd

    2015-03-01

    Over the last decade, caring for patients who are conscious while receiving mechanical ventilator treatment has become common in Scandinavian intensive care units. Therefore, this study aimed to describe anesthetists', nurses', and nursing assistants' experiences of caring for such patients. Nine persons were interviewed. A hermeneutic method inspired by Gadamer's philosophy was used to interpret and analyze the interview text. Staff members found it distressing to witness and be unable to alleviate suffering, leading to ethical conflicts, feelings of powerlessness, and betrayal of the promises made to the patient. They were frustrated about their inability to understand what the patients were trying to say and often turned to colleagues for help. When caring for conscious patients, it takes time to get to know them and establish communication and a trusting relationship.

  2. Cerebrospinal fluid HIV-1 RNA levels in asymptomatic patients with early stage chronic HIV-1 infection: support for the hypothesis of local virus replication.

    PubMed

    García, F; Niebla, G; Romeu, J; Vidal, C; Plana, M; Ortega, M; Ruiz, L; Gallart, T; Clotet, B; Miró, J M; Pumarola, T; Gatell, J M

    1999-08-20

    To assess HIV-1 RNA levels in cerebrospinal fluid (CSF) and their potential correlation with plasma viral load and central nervous system (CNS) HIV-1 infection markers in stable asymptomatic patients with a CD4 T cell count >500x10(6) cells/l. Consecutive patients screened for two trials were eligible for lumbar puncture assessment. At day 0, simultaneous samples of CSF and plasma were obtained and levels of total proteins, albumin, IgG, antibodies against HIV-1 p24 antigen, HIV-1 RNA (using the polymerase chain technique) and white cells were measured. The integrity of the blood-brain barrier was preserved (albumin index > or =7) in 59 out of 70 patients (84%). Intrathecal production of antibodies against HIV-1 p24 antigen was demonstrated in 55 out of 70 individuals (78%). Viral load in CSF was significantly lower than plasma values (3.13+/-0.95 versus 4.53+/-0.53, P = 0.0001). HIV-1 RNA was not detected in CSF in only three of the 70 patients (4%). Overall, there was a significant correlation between plasma and CSF HIV-1 RNA levels (r = 0.43, P = 0.0001); however, in 29 patients (41%) there were significant differences (>1.5 log10 copies/ml) between the viral loads in plasma and CSF. In the multivariate analysis, a high level of protein and white cells in CSF, but not the HIV-1 RNA plasma level, were factors independently associated with a higher level of HIV-1 RNA in CSF (P = 0.0001). HIV-1 RNA can be detected almost always in CSF of asymptomatic patients in early stages of HIV-1 infection including those with a preserved integrity of the blood-brain barrier. The important discrepancies between plasma and CSF viral load, and the independent association between CSF abnormalities and CSF viral load, support the hypothesis of local production of HIV-1.

  3. Applicability of Hepatitis C Virus RNA Viral Load Thresholds for 8-Week Treatments in Patients With Chronic Hepatitis C Virus Genotype 1 Infection.

    PubMed

    Vermehren, Johannes; Maasoumy, Benjamin; Maan, Raoel; Cloherty, Gavin; Berkowski, Caterina; Feld, Jordan J; Cornberg, Markus; Pawlotsky, Jean-Michel; Zeuzem, Stefan; Manns, Michael P; Sarrazin, Christoph; Wedemeyer, Heiner

    2016-05-15

    Interferon-free treatment of chronic hepatitis C virus (HCV) genotype 1 infection may be shortened to 8 weeks in treatment-naive, noncirrhotic patients with baseline HCV RNA levels of <4 or <6 million (M) IU/mL based on post-hoc analyses of phase 3 trial data. The applicability of these viral load thresholds in clinical practice is unknown. Pretreatment and on-treatment serum samples (n = 740) from patients with HCV genotype 1 infection were included for HCV RNA analysis with 2 widely used assays, Cobas AmpliPrep/CobasTaqMan (CAP/CTM) and Abbott RealTime HCV (ART) assays. HCV RNA levels were significantly higher with CAP/CTM than with ART (overall difference, +0.11 log10 IU/mL; P < .001). In treatment-naive, noncirrhotic patients, discordance rates around the clinical cutoffs at 4M and 6M IU/mL were 23% and 18%, respectively. The mean differences between assays in discordant samples were 0.38 (4M) and 0.41 (6M) log10 IU/mL, respectively. Overall, 87% and 95% of treatment-naive, noncirrhotic patients, respectively, had baseline HCV RNA levels below 4M and 6M IU/mL with ART. These rates were significantly higher than those measured with CAP/CTM (64% and 78%, respectively; P < .001). Finally, discordance rates around the proposed thresholds in 2 consecutive samples of the same patient were in the range of 1%-2% for ART and 13%-17% for CAP/CTM. Selection of patients for 8-week regimens on the basis of a single HCV RNA determination may not be reliable because viral load levels around the proposed clinical thresholds show significant interassay and intrapatient variability. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  4. Determinants of survival in patients receiving dialysis in Libya.

    PubMed

    Alashek, Wiam A; McIntyre, Christopher W; Taal, Maarten W

    2013-04-01

    Maintenance dialysis is associated with reduced survival when compared with the general population. In Libya, information about outcomes on dialysis is scarce. This study, therefore, aimed to provide the first comprehensive analysis of survival in Libyan dialysis patients. This prospective multicenter study included all patients in Libya who had been receiving dialysis for >90 days in June 2009. Sociodemographic and clinical data were collected upon enrollment and survival status after 1 year was determined. Two thousand two hundred seventy-three patients in 38 dialysis centers were followed up for 1 year. The majority were receiving hemodialysis (98.8%). Sixty-seven patients were censored due to renal transplantation, and 46 patients were lost to follow-up. Thus, 2159 patients were followed up for 1 year. Four hundred fifty-eight deaths occurred, (crude annual mortality rate of 21.2%). Of these, 31% were due to ischemic heart disease, 16% cerebrovascular accidents, and 16% due to infection. Annual mortality rate was 0% to 70% in different dialysis centers. Best survival was in age group 25 to 34 years. Binary logistic regression analysis identified age at onset of dialysis, physical dependency, diabetes, and predialysis urea as independent determinants of increased mortality. Patients receiving dialysis in Libya have a crude 1-year mortality rate similar to most developed countries, but the mean age of the dialysis population is much lower, and this outcome is thus relatively poor. As in most countries, cardiovascular disease and infection were the most common causes of death. Variation in mortality rates between different centers suggests that survival could be improved by promoting standardization of best practice. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

  5. Thalidomide for Control Delayed Vomiting in Cancer Patients Receiving Chemotherapy.

    PubMed

    Han, Zhengxiang; Sun, Xuan; Jiang, Guan; Du, Xiuping

    2016-11-01

    To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. Randomized, double-blind controlled study. The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the c2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (c2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.

  6. Vascular access in patients receiving hemodialysis in Libya.

    PubMed

    Alashek, Wiam A; McIntyre, Christopher W; Taal, Maarten W

    2012-01-01

    A native arteriovenous fistula (AVF) represents the optimal form of Vascular Access (VA) for patients receiving hemodialysis (HD). In Libya there are several barriers to AVF creation including lack of adequate preparation for dialysis and surgical services. We aimed to conduct the first comprehensive study of VA utilisation in HD patients in Libya. A prospective observational study included all adult patients receiving HD treatment in 25 HD facilities in Libya from May 2009 to Nov 2011. Researchers gathered data regarding VA through interviews with staff and patients as well as medical records. Patients with definitive VA were re-interviewed after 1 year. At baseline the majority of patients (91.9%; n=1573) were using permanent VA in the form of AVF or arteriovenous graft. Patients with permanent VA were more likely to be male and less likely to be diabetic than those with CVCs. Most patients had commenced HD using a temporary CVC (91.8%). VA-related complications were: thrombosis (46.7%), aneurysm (22.6%), infection (11.5%) and haemorrhage (10.2%). Incident VA thrombosis was reported by 14.7% in 1 year. Independent risk factors for incident thrombosis were female gender and diabetes. Hospitalisation for VA related complications was reported by 31.4%. Few patients in Libya initiate HD with definitive VA, but most achieve it thereafter. Improved dialysis preparation and increased provision of surgical services are required to increase the proportion of patients initiating HD with definitive VA and should be a priority in rebuilding health services in Libya after the recent conflict.

  7. [Prescribing drugs to patients receiving out-patient care].

    PubMed

    Garjón Parra, F J

    2009-01-01

    Drug prescription has evolved to deal mainly with chronic diseases. Nowadays, repeating prescriptions using computers results in problems if this is not done with adequate control. Steps proposed for appropriate prescription are: defining the problem; specifying the objective; selecting the drug; initiating therapy with appropriate details; giving information; regular evaluation; considering cost; and using tools to reduce errors. Published recommendations for prescription, which have focused on elderly patients, include: avoiding polypharmacy; carrying out a regular medication review; stopping any current drugs that are not indicated and prescribing new drugs that have a clear indication; avoiding drugs that have deleterious effects; using dosages that are suitable for the age and renal function; using simple drug regimes and appropriate administration systems; considering non-pharmacological treatments; limiting the number of practitioners prescribing for each patient; and avoiding treating adverse drug reactions with further drugs. Examples of compliance with those recommendations in the Navarre Health Service, extracted from the prescription information system, are provided. The measures for improving prescription are: education, auditing, collaboration between health professionals and use of electronic tools.

  8. Gonadal dysfunction and infertility in kidney transplant patients receiving sirolimus.

    PubMed

    Boobes, Yousef; Bernieh, Bassam; Saadi, Hussein; Raafat Al Hakim, M; Abouchacra, Samra

    2010-06-01

    Sirolimus is an immunosupressor of the mammalian target of rapamycin inhibitors (mTOR-I) group. Recent studies have emphasized a potential impact of sirolimus on male gonadal function. We report our clinical experience with sirolimus-induced gonadal dysfunction and infertility in both male and female kidney transplant patients. Of the 170 kidney transplant patients, nine (5.3%) patients (six males and three females) were receiving sirolimus. Follow-up data for two male patients were not available. The one unmarried female patient developed amenorrhea post-transplantation and had resumption of her menstrual cycles after discontinuation of sirolimus. The remaining six married patients (four males and two females), who all had fathered or conceived children in the pre-transplantation period, developed gonadal dysfunction and infertility on average 5-12 months after transplantation. Sirolimus was discontinued in all four male patients with full recovery of the oligo/azospermia and restoration of fertility. Both married female patients developed amenorrhea post-transplantation. Sirolimus was discontinued in one female patient with resumption of her menstrual cycles. In this small population of patients treated with sirolimus, the prevalence rate of reversible gonadal dysfunction and infertility was significant in both males and females. Infertility secondary to sirolimus is under-diagnosed and should be studied further.

  9. Polypharmacy in Older Patients ≥70 Years Receiving Palliative Radiotherapy.

    PubMed

    Nieder, Carsten; Mannsăker, Bărd; Pawinski, Adam; Haukland, Ellinor

    2017-02-01

    Many older cancer patients receive five or more daily medications (polypharmacy). The purpose of this study was to assess the prevalence of polypharmacy in older patients undergoing palliative radiotherapy and its influence on the risk of being unable to complete the prescribed number of fractions, as well as the 30-day mortality and overall survival. Retrospective review of 289 patients aged 70 years or older. The median and mean Charlson comorbidity index (11) was 2, ranging between 0-7 (presently treated cancer not included). The median and mean number of daily medications was 7, ranging between 0-18. Only 27% of patients used less than 5 daily medications. Corticosteroids were used by 59% of the patients and opioid analgesics by 55%. Comorbidity, but also symptom severity, as indexed by pain medication, correlated significantly with the prevalence of polypharmacy. In multivariate analysis, neither polypharmacy nor use of corticosteroids or opioid analgesics influenced overall survival. No trends were seen for 30-day mortality or failure to complete radiotherapy. Polypharmacy is a common phenomenon in older patients receiving palliative radiotherapy and it does not predict adverse radiotherapy outcomes. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Expansion in CD39+ CD4+ Immunoregulatory T Cells and Rarity of Th17 Cells in HTLV-1 Infected Patients Is Associated with Neurological Complications

    PubMed Central

    Hasenkrug, Aaron M.; Bruno, Fernanda R.; Carvalho, Karina I.; Wynn-Williams, Harry; Neto, Walter K.; Sanabani, Sabri S.; Segurado, Aluisio C.; Nixon, Douglas F.; Kallas, Esper G.

    2013-01-01

    HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4+ T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. The CD39 ectonucleotidase receptor is expressed on CD4+ T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39+CD25+) and effector (CD39+CD25−) function. Here, we investigated the expression of CD39 on CD4+ T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. The frequency of CD39+ CD4+ T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39+CD25− CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39+CD25+ regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39−CD25+ T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4+ T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4+ T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of

  11. Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms.

    PubMed

    Fuchs, D; Möller, A A; Reibnegger, G; Stöckle, E; Werner, E R; Wachter, H

    1990-01-01

    We investigated serum neopterin, tryptophan, and kynurenine concentrations in 23 HIV-1 seropositive patients (Walter Reed Stage 4-6). Ten patients presented with polyneuropathy and three with dementia, one of the patients with dementia also had polyneuropathy and dementia. We found significant associations between lower trytophan concentrations and neurologic/psychiatric symptoms. The negative correlation of tryptophan with kynurenine and neopterin concentrations indicates activity of indoleamine 2,3-dioxygenase (IDO) in patients. IDO can be induced by cytokines such as interferon-gamma and therefore low tryptophan levels may result from chronic immune stimulation in HIV-1 seropositives.

  12. Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1.

    PubMed

    Mothe, Beatriz; Climent, Nuria; Plana, Montserrat; Rosàs, Miriam; Jiménez, José Luis; Muñoz-Fernández, María Ángeles; Puertas, María C; Carrillo, Jorge; Gonzalez, Nuria; León, Agathe; Pich, Judit; Arnaiz, Joan Albert; Gatell, Jose M; Clotet, Bonaventura; Blanco, Julià; Alcamí, José; Martinez-Picado, Javier; Alvarez-Fernández, Carmen; Sánchez-Palomino, Sonsoles; Guardo, Alberto C; Peña, José; Benito, José M; Rallón, Norma; Gómez, Carmen E; Perdiguero, Beatriz; García-Arriaza, Juan; Esteban, Mariano; López Bernaldo de Quirós, Juan Carlos; Brander, Christian; García, Felipe

    2015-01-01

    The safety, immunogenicity, impact on the latent reservoir and rebound of viral load after therapeutic HIV-1 vaccination with recombinant modified vaccinia Ankara-based (MVA-B) HIV-1 vaccine expressing monomeric gp120 and the fused Gag-Pol-Nef polyprotein of clade B with or without a drug to reactivate latent HIV-1 (disulfiram) were assessed. HIV-1-infected patients were randomized to receive three injections of MVA-B (n = 20) or placebo (n = 10). Twelve patients (eight who received vaccine and four who were given placebo) received a fourth dose of MVA-B followed by 3 months of disulfiram. Combined ART (cART) was discontinued 8 weeks after the last dose of MVA-B. Clinical Trials.gov identifier: NCT01571466. MVA-B was safe and well tolerated. A minor, but significant, increase in the T cell responses targeting vaccine inserts of Gag was observed [a median of 290, 403 and 435 spot-forming-cells/10(6) PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P = 0.02 and P = 0.04]. After interruption of cART, a modest delay in the rebound of the plasma viral load in participants receiving vaccine but not disulfiram was observed compared with placebo recipients (P = 0.01). The dynamics of the viral load rebound did not change in patients receiving MVA-B/disulfiram. No changes in the proviral reservoir were observed after disulfiram treatment. MVA-B vaccination was a safe strategy to increase Gag-specific T cell responses in chronically HIV-1-infected individuals, but it did not have a major impact on the latent reservoir or the rebound of plasma viral load after interruption of cART when given alone or in combination with disulfiram. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Hospice Care: What Services Do Patients and Their Families Receive?

    PubMed Central

    Carlson, Melissa D A; Morrison, R Sean; Holford, Theodore R; Bradley, Elizabeth H

    2007-01-01

    Objective To determine the degree to which patients and families enrolled with hospice received services across key categories of palliative care, the extent of hospice-level variability in services delivered, and changes over time in services delivered. Data Source Nationally representative sample of 9,409 discharged patients from 2,066 hospices in the National Home and Hospice Care Survey. Study Design Observational, cross-sectional study conducted from 1992 to 2000. The primary outcome is the receipt of services across five key categories of palliative care: nursing care, physician care, medication management, psychosocial care, and caregiver support. Data Collection Data were obtained via interview with the hospice staff member most familiar with the patient's care, in conjunction with medical record review. Principle Findings In 2000, 22 percent of patients enrolled with hospice received services across five key categories of palliative care. There was marked variation across hospices in service delivery. One-third of hospices provided patients and families services in one or two of the five key categories of palliative care, whereas 14 percent of hospices provided services across five key categories of palliative care. In multivariable analysis, the odds of receiving any additional hospice service was significantly greater in later compared with earlier years (odds ratio = 1.10, 95 percent confidence interval 1.01–1.20). Nevertheless, the percentages of patients in 2000 receiving medication management (59 percent), respite care (7 percent), and physician services (30 percent) remained low. Conclusions Hospice care for patients and families varies substantially across hospices. Whereas some hospices provide services across the key categories of palliative care, other hospices do not provide this breadth of services. Greater understanding of the causes of variation in service delivery as well as its impact on patient and family outcomes and satisfaction with

  14. Dental extraction in patients receiving dual antiplatelet therapy

    PubMed Central

    Sánchez-Palomino, Paulino; Sánchez-Cobo, Paulino; Rodriguez-Archilla, Alberto; González-Jaranay, Maximino; Moreu, Gerardo; Calvo-Guirado, José-Luis; Peñarrocha-Diago, Miguel

    2015-01-01

    Background Dual anti platelet therapy consists of administering antiplatelet (antiaggregant) drugs (clopidogrel and aspirin) to prevent thrombotic processes, as a preventative measure in patients with acute coronary disease, or in patients subjected to percutaneous coronary intervention. Objectives The purpose of this study was to evaluate the efficacy of a protocol for performing dental extraction in patients receiving dual anti platelet therapy. Material and Methods Thirty-two patients undergoing dental extractions were included in the study. The variables evaluated were: collagen-epinephrine fraction, collagen- adenosine diphosphate fraction, surgical surface, post-surgical measures, and adverse effects. Alveolar sutures and gauzes impregnated with an antifibrinolytic agent (tranexamic acid), which the patient pressed in place for 30 minutes, were applied to all patients as post-surgical measures. Descriptive statistics were calculated and analyzed with Student’s t-test to compare pairs of quantitative variables; simple regression analysis was performed using Pearson’s correlation coefficient. Statistical significance was set at p<0.05. Results Collagen/epinephrine fraction was 264.53±55.624 seconds with a range of 135 to 300 seconds, and collagen/ADP fraction was 119.41±44.216 seconds, both values being higher than normal. As a result of the post-surgical measures taken, no patients presented postoperative bleeding, hematoma or infection. Conclusions Dental extraction was safe for patients receiving dual anti-platelet therapy when using sutures and gauze impregnated with tranexamic acid, which the patient pressed in place for 30 minutes. Key words: Aspirin, clopidogrel, tranexamic acid, dental extraction, platelet function. PMID:26241454

  15. Mortality and morbidity among HIV type-1-infected patients during the first 5 years of a multicountry HIV workplace programme in Africa.

    PubMed

    Van der Borght, Stefaan F; Clevenbergh, Philippe; Rijckborst, Henk; Nsalou, Paul; Onyia, Ngozi; Lange, Joep M; de Wit, Tobias F Rinke; Van der Loeff, Maarten F Schim

    2009-01-01

    This study aimed to evaluate the effectiveness of an HIV workplace programme in sub-Saharan Africa. The international brewing company, Heineken, introduced an HIV workplace programme in its African subsidiaries in 2001. Beneficiaries from 16 sites in 5 countries were eligible. HIV type-1 (HIV-1)-infected individuals were assessed clinically and immunologically, and started highly active antiretroviral therapy (HAART) if they had AIDS or had a CD4+ T-cell count <300 cells/microl. In this cohort, study patients were followed-up for vital status, new AIDS events, CD4+ T-cell count and haemoglobin. Over the first 5 years of the programme, 431 adults were found to be HIV-1-infected. The mortality rate among those not yet taking HAART was 2.6 per 100 person-years of observation (pyo). By October 2006, 249 patients had started HAART at a median CD4+ T-cell count of 170 cells/microl; 59 (23.7%) patients were in CDC stage C. Among patients on HAART, 25 died and 7 were lost to follow-up. The mortality rate was 3.7 per 100 pyo overall, 14 per 100 pyo in the first 16 weeks and 2.5 per 100 pyo thereafter (P < 0.0001). At 4 years after start of treatment, 89% of patients were known to be alive. The CD4+ T-cell count increased by a median of 153 and 238 cells/microl after 1 and 4 years of HAART, respectively. In this HIV workplace programme in sub-Saharan Africa, long-term high survival was achieved.

  16. Clinical utility of the ARCHITECT HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection.

    PubMed

    Vermehren, Johannes; Susser, Simone; Berger, Annemarie; Perner, Dany; Peiffer, Kai-Henrik; Allwinn, Regina; Zeuzem, Stefan; Sarrazin, Christoph

    2012-09-01

    Virologic response-monitoring is essential for determining therapy duration in patients with chronic hepatitis C virus (HCV) infection. This is usually performed using highly sensitive HCV-RNA assays. However, HCV-RNA assays are time-consuming, expensive and require highly trained personnel. Quantitative determination of HCV core-antigen (HCVAg) levels may be used to supplement treatment monitoring. The clinical utility of the ARCHITECT HCV Ag assay (Abbott Diagnostics) for response-guided therapy was investigated. We analyzed serum from 160 patients with HCV genotype 1 infection who had been treated with peg-interferon alfa-2b/ribavirin. HCVAg levels were determined at baseline, weeks 1, 2, 4 and 12. HCVAg levels were compared to those obtained with HCV-RNA assays: VERSANT HCV Quantitative 3.0 (bDNA) and Qualitative (TMA, both Siemens Healthcare) assay and the Abbott RealTime HCV assay (ART; Abbott Diagnostics). Baseline HCVAg levels correlated well with HCV-RNA as assessed by bDNA (r=0.91; p<0.0001) and ART (r=0.92; p<0.0001), respectively. Patients with undetectable HCVAg levels at week 1 had a 90.9% probability (positive predictive value) to achieve a rapid virologic response (HCV-RNA undetectable at week 4) based on TMA and 86.4% based on ART, respectively. Patients with less than 1 log(10) reduction in HCVAg between baseline and week 12 had a 90% probability (negative predictive value) to achieve a nonresponse (<2 log(10) decline in HCV-RNA between baseline and week 12) based on bDNA and 100% based on ART, respectively. Determination of HCVAg may be useful for antiviral response-monitoring in patients with HCV genotype 1 infection. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Patients receiving frequent hemodialysis have better health-related quality of life compared to patients receiving conventional hemodialysis.

    PubMed

    Garg, Amit X; Suri, Rita S; Eggers, Paul; Finkelstein, Fredric O; Greene, Tom; Kimmel, Paul L; Kliger, Alan S; Larive, Brett; Lindsay, Robert M; Pierratos, Andreas; Unruh, Mark; Chertow, Glenn M

    2017-03-01

    Most patients with end-stage kidney disease value their health-related quality of life (HRQoL) and want to know how it will be affected by their dialysis modality. We extended the findings of two prior clinical trial reports to estimate the effects of frequent compared to conventional hemodialysis on additional measures of HRQoL. The Daily Trial randomly assigned 245 patients to receive frequent (six times per week) or conventional (three times per week) in-center hemodialysis. The Nocturnal Trial randomly assigned 87 patients to receive frequent nocturnal (six times per week) or conventional (three times per week) home hemodialysis. All patients were on conventional hemodialysis prior to randomization, with an average feeling thermometer score of 70 to 75 (a visual analog scale from 0 to 100 where 100 is perfect health), an average general health scale score of 40 to 47 (a score from 0 to 100 where 100 is perfect health), and an average dialysis session recovery time of 2 to 3 hours. Outcomes are reported as the between-treatment group differences in one-year change in HRQoL measures and analyzed using linear mixed effects models. After one year in the Daily Trial, patients assigned to frequent in-center hemodialysis reported a higher feeling thermometer score, better general health, and a shorter recovery time after a dialysis session compared to standard thrice-weekly dialysis. After one year in the Nocturnal Trial, patients assigned to frequent home hemodialysis also reported a shorter recovery time after a dialysis session, but no statistical difference in their feeling thermometer or general health scores compared to standard home dialysis schedules. Thus, patients receiving day or nocturnal hemodialysis on average recovered approximately one hour earlier from a frequent compared to conventional hemodialysis session. Patients treated in an in-center dialysis facility reported better HRQoL with frequent compared to conventional hemodialysis.

  18. Blastomycosis and Histoplasmosis in a Patient with Glioblastoma Receiving Temozolomide.

    PubMed

    Jbeli, Aiham H; Yu, John

    2016-10-01

    Malignant glioblastoma multiform (GBM) is the most common primary malignancy of the brain in the U.S. Temozolomide (TMZ) is the cornerstone of management along with surgical resection and radiotherapy. Because of the reduction in the CD4+ lymphocyte count as a side effect of TMZ use, this patient population is under risk for opportunistic infections like Pneumocystis jiroveci. A male patient with newly diagnosed glioblastoma multiform presented with non-productive cough and chest pain. Before presentation, the patient received the standard therapy including surgical resection, radiation and TMZ. Computerized tomography of the chest showed a very large cavitary lesion in the upper segment of the right lower lobe and multiple nodular lesions with some starting to cavitate. Cytology of the bronchioalveolar lavage with special stain showed large, broad based budding yeast-like cells, morphologically consistent with blastomyces and macrophages filled with yeast-like forms, morphologically consistent with histoplasma. The patient was treated with intraconazole intended for 12 months. To the best of our knowledge, our case represents the first documented case of lung infection with both blastomyces and histoplasma in a patient after receiving TMZ for newly diagnosed GBM. Copyright© South Dakota State Medical Association.

  19. The Evaluation of Carotid Atherosclerosis in Patients with the HIV-1 Infection: The Role of the Antiretroviral Therapy

    PubMed Central

    P.N., Suparna; Achappa, Basavaprabhu; B., Unnikrishnan; Madi, Deepak; Chowta, Mukta N.; Ramapuram, John T; Rao, Satish; Mahalingam, Soundarya

    2013-01-01

    Background and Objective: The recognition and the assessment of the carotid intimal thickness helps in predicting the risk of the cardiovascular events in Human Immunodeficiency Virus (HIV) infected patients who are on Antiretroviral Therapy (ART). The objective of this study was to assess and compare the carotid intimal thickness in HIV positive individuals who were on antiretroviral therapy with HIV positive individuals who were not on anti-retroviral therapy. Subjects and Methods: All the HIV positive individuals who were 20 years old and above, who had been diagnosed by the National AIDS Control Organization (NACO) guidelines were included in the study. The HIV positive individuals who were diagnosed with diabetes mellitus and hypertension were excluded from the study. The study subjects were divided into 2 groups i.e. HIV patients who were on anti-retroviral therapy and HIV patients who were not on anti-retroviral therapy. The patients had to be on anti-retroviral therapy for a minimum of 6 months for them to be included in the first group. The data was collected by using a semi structured, pre-tested proforma, which included the demographic details, the duration of the HIV infection, details of the antiretroviral treatment, a history of smoking/ alcohol consumption and details on the assessments of the metabolic syndrome. Results: A total of 42 patients were included in the study. Among them, 28 were males (66.7%) and 14 were females (33.3%). Twenty six patients were on ART and the remaining patients were treatment naive. There were significant differences with regards to their age and the duration of the HIV infection, which was longer in the patients who were on ART (p= 0.049, p=0.003 respectively). The Body Mass Index (BMI), the waist: hip ratio, the mid-arm circumference, the waist circumference, the skin fold thickness and the carotid intimal-media thickness were higher in the HIV patients who were on ART as compared to those in the treatment naive

  20. Abnormal contingent negative variation in HIV patients receiving antiretroviral therapy

    PubMed Central

    Chao, Linda L.; Cardenas, Valerie A.; Meyerhoff, Dieter J.; Rothlind, Johannes C.; Flenniken, Derek L.; Lindgren, Joselyn A.; Weiner, Michael W.

    2009-01-01

    The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virally suppressed patients and controls on neuropsychological measures of psychomotor speed, selective attention and mental flexibility. These results suggest that antiretroviral therapy may not be effective in protecting cortical and subcortical structures against HIV-related neuropathology, regardless of immune function. However, the benefits of antiretroviral therapy on immune function appear to facilitate neurocognitive performance. PMID:14600507

  1. Inhibition of replication of primary HIV-1 isolates in huPBL-NOD/Scid mice by antibodies from HIV-1 infected patients.

    PubMed

    Steyaert, Sophia; Heyndrickx, Leo; Verhoye, Lieven; Vermoesen, Tine; Donners, Helen; Fransen, Katrien; Van Wanzeele, Filip; Vandergucht, Beatrijs; Vanham, Guido; Leroux-Roels, Geert; Vanlandschoot, Peter

    2007-08-01

    Although a limited number of HIV-infected patients have broadly neutralizing antibodies, it has not been examined whether these antibodies can protect against infection with primary virus in vivo. Here we screened the plasma of 23 HIV-1-infected patients for broadly neutralizing antibodies. Purified antibodies from subjects with broad and more narrow responses were administered to huPBL-NOD/Scid mice that were subsequently challenged with primary viruses of clade A, B and CRF01_AE. Although we observed a lack of correlation between the data from the in vitro neutralization assay and the results from the passive immunization experiments, we report for the first time that antibodies from HIV-infected persons can inhibit replication of primary virus isolates in an animal model.

  2. Patient Preferences for Receiving Reports of Test Results.

    PubMed

    LaRocque, Jeannine R; Davis, Christina L; Tan, Tina P; D'Amico, Frank J; Merenstein, Daniel J

    2015-01-01

    The general public's preferences for modes of communication (other than in-person communication) for medical test results were investigated. We hypothesized that patients would prefer a variety of methods to receive common tests results (blood cholesterol and colonoscopy) compared with genetics test results. This study was a cross-sectional survey. A total of 409 participants responded to the survey. Among these participants, ≥50% reported that they were comfortable receiving results for a blood cholesterol test or colonoscopy via 4 of the 7 non-in-person communication methods (password-protected website, personal voicemail, personal E-mail, and letter were preferred over home voicemail, fax, and mobile phone text message). In comparison, >50% of participants were comfortable with only 1 non-in-person communication method for non-HIV sexually transmitted infections (STIs) and none for genetic tests. Patients were least comfortable receiving any information via fax, regardless of test type. There were statistical differences among comfort levels for blood cholesterol and colonoscopy tests and both STIs and genetic testing for personal voicemail, personal E-mail, mobile phone text message, and password-protected website, but there were no differences between STIs and genetic testing. No correlation was found between "familiarity" with test and "comfort" of receiving information about specific test. Participants demonstrated preferences in how they received test results by non-in-person communication methods, preferring personal E-mail and password-protected websites, but did not prefer fax. Importantly, participants also demonstrated that preference was dependent on test type. © Copyright 2015 by the American Board of Family Medicine.

  3. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.

    PubMed

    Afdhal, Nezam; Zeuzem, Stefan; Kwo, Paul; Chojkier, Mario; Gitlin, Norman; Puoti, Massimo; Romero-Gomez, Manuel; Zarski, Jean-Pierre; Agarwal, Kosh; Buggisch, Peter; Foster, Graham R; Bräu, Norbert; Buti, Maria; Jacobson, Ira M; Subramanian, G Mani; Ding, Xiao; Mo, Hongmei; Yang, Jenny C; Pang, Phillip S; Symonds, William T; McHutchison, John G; Muir, Andrew J; Mangia, Alessandra; Marcellin, Patrick

    2014-05-15

    In phase 2 studies, treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus (HCV) genotype 1 infection. We conducted a phase 3, open-label study involving previously untreated patients with chronic HCV genotype 1 infection. Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Of the 865 patients who underwent randomization and were treated, 16% had cirrhosis, 12% were black, and 67% had HCV genotype 1a infection. The rates of sustained virologic response were 99% (95% confidence interval [CI], 96 to 100) in the group that received 12 weeks of ledipasvir-sofosbuvir; 97% (95% CI, 94 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin; 98% (95% CI, 95 to 99) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 97 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. The most common adverse events were fatigue, headache, insomnia, and nausea. Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.).

  4. Cancer and Fertility Program Improves Patient Satisfaction With Information Received

    PubMed Central

    Thom, Bridgette; Benedict, Catherine; Carter, Jeanne; Corcoran, Stacie; Dickler, Maura N.; Goodman, Karyn A.; Margolies, Allison; Matasar, Matthew J.; Noy, Ariela; Goldfarb, Shari B.

    2016-01-01

    Purpose A cancer and fertility program was established at a large cancer center to support clinicians in discussing treatment-related fertility risks and fertility preservation (FP) options with patients and in referring patients to reproductive specialists. The program provides resources, clinician education, and fertility clinical nurse specialist consultation. This study evaluated the program’s impact on patient satisfaction with information received. Patients and Methods Retrospective cross-sectional surveys assessed satisfaction before (cohort 1 [C1]) and after (cohort 2 [C2]) program initiation. Questionnaires were investigator-designed, gender-specific, and anonymous. Results Most C1 (150 males, 271 females) and C2 (120 males, 320 females) respondents were 2 years postdiagnosis; the most frequently reported cancers were testicular, breast, and lymphoma. A significant difference in satisfaction with the amount of information received was seen between C1 and C2. For males, satisfaction with information on fertility risks was high in both cohorts but significantly greater in C2 for information on sperm banking (χ2 = 9.3, P = .01) and finding a sperm bank (χ2 = 13.3, P = .001). For females, satisfaction with information was significantly greater in C2 for information on fertility risks (χ2 = 62.1, P < .001), FP options (χ2 = 71.9, P < .001), help with decision making (χ2 = 80.2, P < .001), and finding a reproductive endocrinologist (χ2 = 60.5, P < .001). Among patients who received and read information materials, 96% of males and 99% of females found them helpful. Among C2 females, fertility clinical nurse specialist consultation was associated with significantly greater satisfaction with information on FP options (χ2 = 11.2, P = .004), help with decision making (χ2 = 10.4, P = .006), and finding a reproductive endocrinologist (χ2 = 22.6, P < .001), with 10% reporting lack of knowledge as a reason for not pursuing FP. Conclusion Improvements in

  5. Pharmacokinetics of Peramivir in an Adolescent Patient Receiving Continuous Venovenous Hemodiafiltration.

    PubMed

    Dillon, Ryan C; Witcher, Robert; Cies, Jeffrey J; Moore, Wayne S; Chopra, Arun

    2017-01-01

    Critically ill patients requiring renal replacement therapy commonly experience pharmacokinetic alterations. This case report describes the pharmacokinetics of peramivir (Rapivab, BioCryst Pharmaceuticals, Inc, Durham, NC), the first US Food and Drug Administration-approved intravenous neuraminidase inhibitor for the treatment of influenza, in an adolescent patient receiving continuous renal replacement therapy (CRRT). A 49.5-kg, 17-year-old Caucasian female presented with fever, cough, and persistent hypoxia. She quickly progressed to acute respiratory and renal failure in the setting of viral septic shock as a result of a severe influenza H1N1 infection. On hospital day 3, therapy was switched from oseltamivir (Tamiflu, Roche Laboratories Inc, Nutley, NJ) to peramivir owing to the concern for inadequate enteral absorption. On the third day of peramivir treatment, at a dose of 200 mg daily, peramivir serum concentrations revealed a smaller peak concentration, larger volumes of distribution, similar 24-hour area under the curve, and a shorter half-life as compared to adult patients with normal renal function. This illustrated the significant differences in pharmacokinetics when administered in the setting of CRRT. The patient had resolution of viral infection as evidenced by negative respiratory viral panel polymerase chain reaction at hospital day 14 and was eventually discharged at her baseline.

  6. Pharmacokinetics of Peramivir in an Adolescent Patient Receiving Continuous Venovenous Hemodiafiltration

    PubMed Central

    Witcher, Robert; Cies, Jeffrey J.; Moore, Wayne S.; Chopra, Arun

    2017-01-01

    Critically ill patients requiring renal replacement therapy commonly experience pharmacokinetic alterations. This case report describes the pharmacokinetics of peramivir (Rapivab, BioCryst Pharmaceuticals, Inc, Durham, NC), the first US Food and Drug Administration–approved intravenous neuraminidase inhibitor for the treatment of influenza, in an adolescent patient receiving continuous renal replacement therapy (CRRT). A 49.5-kg, 17-year-old Caucasian female presented with fever, cough, and persistent hypoxia. She quickly progressed to acute respiratory and renal failure in the setting of viral septic shock as a result of a severe influenza H1N1 infection. On hospital day 3, therapy was switched from oseltamivir (Tamiflu, Roche Laboratories Inc, Nutley, NJ) to peramivir owing to the concern for inadequate enteral absorption. On the third day of peramivir treatment, at a dose of 200 mg daily, peramivir serum concentrations revealed a smaller peak concentration, larger volumes of distribution, similar 24-hour area under the curve, and a shorter half-life as compared to adult patients with normal renal function. This illustrated the significant differences in pharmacokinetics when administered in the setting of CRRT. The patient had resolution of viral infection as evidenced by negative respiratory viral panel polymerase chain reaction at hospital day 14 and was eventually discharged at her baseline.

  7. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study.

    PubMed

    Roth, David; Nelson, David R; Bruchfeld, Annette; Liapakis, AnnMarie; Silva, Marcelo; Monsour, Howard; Martin, Paul; Pol, Stanislas; Londoño, Maria-Carlota; Hassanein, Tarek; Zamor, Philippe J; Zuckerman, Eli; Wan, Shuyan; Jackson, Beth; Nguyen, Bach-Yen; Robertson, Michael; Barr, Eliav; Wahl, Janice; Greaves, Wayne

    2015-10-17

    Chronic hepatitis C virus (HCV) infection in patients with stage 4-5 chronic kidney disease increases the risk of death and renal graft failure, yet patients with hepatitis C and chronic kidney disease have few treatment options. This study assesses an all-oral, ribavirin-free regimen in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease. In this phase 3 randomised study of safety and observational study of efficacy, patients with HCV genotype 1 infection and chronic kidney disease (stage 4-5 with or without haemodialysis dependence) were randomly assigned to receive grazoprevir (100 mg, NS3/4A protease inhibitor) and elbasvir (50 mg, NS5A inhibitor; immediate treatment group) or placebo (deferred treatment group) once daily for 12 weeks. Randomisation was done centrally with an interactive voice response system. An additional cohort of patients who were not randomised received the same regimen open-label and underwent intensive pharmacokinetic sampling. The primary efficacy outcome was a non-randomised comparison of sustained virological response at 12 weeks (SVR12) after the end of therapy for the combined immediate treatment group and the pharmacokinetic population with a historical control. The primary safety outcome was a randomised comparison between the immediate treatment group and the deferred treatment group. After 4 weeks of follow-up (study week 16), unmasking occurred and patients in the deferred treatment group received grazoprevir and elbasvir. The primary efficacy hypothesis was tested at a two-sided significance level (type I error) of 0·05 using an exact test for a binomial proportion. Safety event rates were compared between immediate treatment and deferred treatment groups using the stratified Miettinen and Nurminen method with baseline dialysis status as the strata. The study is registered at ClinicalTrials.gov, number NCT02092350. 224 patients were randomly assigned to the immediate treatment group with grazoprevir

  8. Phage Neutralization by Sera of Patients Receiving Phage Therapy

    PubMed Central

    Żaczek, Maciej; Weber-Dąbrowska, Beata; Międzybrodzki, Ryszard; Kłak, Marlena; Fortuna, Wojciech; Letkiewicz, Sławomir; Rogóż, Paweł; Szufnarowski, Krzysztof; Jończyk-Matysiak, Ewa; Owczarek, Barbara; Górski, Andrzej

    2014-01-01

    Abstract The aim of our investigation was to verify whether phage therapy (PT) can induce antiphage antibodies. The antiphage activity was determined in sera from 122 patients from the Phage Therapy Unit in Wrocław with bacterial infections before and during PT, and in sera from 30 healthy volunteers using a neutralization test. Furthermore, levels of antiphage antibodies were investigated in sera of 19 patients receiving staphylococcal phages and sera of 20 healthy volunteers using enzyme-linked immunosorbent assay. The phages were administered orally, locally, orally/locally, intrarectally, or orally/intrarectally. The rate of phage inactivation (K) estimated the level of phages' neutralization by human sera. Low K rates were found in sera of healthy volunteers (K≤1.73). Low K rates were detected before PT (K≤1.64). High antiphage activity of sera K>18 was observed in 12.3% of examined patients (n=15) treated with phages locally (n=13) or locally/orally (n=2) from 15 to 60 days of PT. High K rates were found in patients treated with some Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis phages. Low K rates were observed during PT in sera of patients using phages orally (K≤1.04). Increased inactivation of phages by sera of patients receiving PT decreased after therapy. These results suggest that the antiphage activity in patients' sera depends on the route of phage administration and phage type. The induction of antiphage activity of sera during or after PT does not exclude a favorable result of PT. PMID:24893003

  9. Descriptive Study of Patients Receiving Excision and Radiotherapy for Keloids

    SciTech Connect

    Speranza, Giovanna Sultanem, Khalil M.D.; Muanza, Thierry

    2008-08-01

    Purpose: To review and describe our institution's outcomes in patients treated with external beam radiotherapy after keloid excision. Methods and Materials: This was a retrospective study. Patients who received radiotherapy between July 1994 and January 2004 after keloid excision were identified. A questionnaire was mailed regarding sociodemographic factors, early and late radiation toxicities, the need for additional therapy, and satisfaction level. All patients had received a total of 15 Gy in three daily 5-Gy fractions. Treatment started within 24 h after surgery and was delivered on a Siemens orthovoltage machine. The data were analyzed using the STATA statistical package. Results: A total of 234 patients were approached. The response rate was 41%, and 75% were female. The mean age was 36.5 years (range, 16-69 years). The patients were mainly of European (53.1%) or African (19.8%) descent. For early toxicity outcomes, 54.2% reported skin redness and 24% reported skin peeling. For late toxicity outcomes, 27% reported telangiectasia and 62% reported permanent skin color changes. No association was found with gender, skin color, or age for the late toxicity outcomes. Of the patients responding, 14.6% required adjuvant treatment. On a visual scale of 1-10 for the satisfaction level, 60% reported a satisfaction level of {>=}8. Telangiectasia was the most significant predictor of a low satisfaction level ({<=}3, p < 0.005). Conclusion: The results of our study have shown that orthovoltage-based radiotherapy after surgical excision for keloids is a good method for the prevention of relapse. It is well tolerated, causes little toxicity, and leads to a high patient satisfaction level.

  10. Phage neutralization by sera of patients receiving phage therapy.

    PubMed

    Łusiak-Szelachowska, Marzanna; Zaczek, Maciej; Weber-Dąbrowska, Beata; Międzybrodzki, Ryszard; Kłak, Marlena; Fortuna, Wojciech; Letkiewicz, Sławomir; Rogóż, Paweł; Szufnarowski, Krzysztof; Jończyk-Matysiak, Ewa; Owczarek, Barbara; Górski, Andrzej

    2014-08-01

    The aim of our investigation was to verify whether phage therapy (PT) can induce antiphage antibodies. The antiphage activity was determined in sera from 122 patients from the Phage Therapy Unit in Wrocław with bacterial infections before and during PT, and in sera from 30 healthy volunteers using a neutralization test. Furthermore, levels of antiphage antibodies were investigated in sera of 19 patients receiving staphylococcal phages and sera of 20 healthy volunteers using enzyme-linked immunosorbent assay. The phages were administered orally, locally, orally/locally, intrarectally, or orally/intrarectally. The rate of phage inactivation (K) estimated the level of phages' neutralization by human sera. Low K rates were found in sera of healthy volunteers (K ≤ 1.73). Low K rates were detected before PT (K ≤ 1.64). High antiphage activity of sera K > 18 was observed in 12.3% of examined patients (n = 15) treated with phages locally (n = 13) or locally/orally (n = 2) from 15 to 60 days of PT. High K rates were found in patients treated with some Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis phages. Low K rates were observed during PT in sera of patients using phages orally (K ≤ 1.04). Increased inactivation of phages by sera of patients receiving PT decreased after therapy. These results suggest that the antiphage activity in patients' sera depends on the route of phage administration and phage type. The induction of antiphage activity of sera during or after PT does not exclude a favorable result of PT.

  11. [Pharmaceutical care program for pediatric patients receiving antiretroviral therapy].

    PubMed

    Barrueco, N; Castillo, I; Ais, A; Martínez, C; Sanjurjo, M

    2005-01-01

    To present a pharmaceutical care program for pediatric patients receiving antiretroviral therapy. In order to establish the pharmaceutical care procedure, papers published up to 2004 on the pharmaceutical care provided to patients receiving antiretroviral therapy were reviewed through a search in Medline and the journal Farmacia Hospitalaria. In addition, bibliographic references that can be systematically used to analyze the pharmacotherapy of each patient have been selected. The pharmaceutical care procedure is divided in three stages (data collection, analysis of the pharmacotherapeutic profile and resolution of the drug-related problems identified) that take place through a semi-structured type of interview. In order to systematize the role of the pharmacist, a table with information on antiretroviral drugs used in Pediatrics was created, as well as an information three-page leaflet and a data collection form. The program includes the goals of the pharmaceutical care process as defined in the recommendations of GESIDA-SEFH-National AIDS Plan 2004 and systematizes the proposed intervention strategies, in an attempt to provide the patient and the caregiver with the information required for an optimum management, in the most comprehensive way and tailored to their individual characteristics.

  12. Immune and Viral Correlates of “Secondary Viral Control” after Treatment Interruption in Chronically HIV-1 Infected Patients

    PubMed Central

    Van Gulck, Ellen; Bracke, Lotte; Heyndrickx, Leo; Coppens, Sandra; Atkinson, Derek; Merlin, Céline; Pasternak, Alexander; Florence, Eric; Vanham, Guido

    2012-01-01

    Upon interruption of antiretroviral therapy, HIV-infected patients usually show viral load rebound to pre-treatment levels. Four patients, hereafter referred to as secondary controllers (SC), were identified who initiated therapy during chronic infection and, after stopping treatment, could control virus replication at undetectable levels for more than six months. In the present study we set out to unravel possible viral and immune parameters or mechanisms of this phenomenon by comparing secondary controllers with elite controllers and non-controllers, including patients under HAART. As candidate correlates of protection, virus growth kinetics, levels of intracellular viral markers, several aspects of HIV-specific CD4+ and CD8+ T cell function and HIV neutralizing antibodies were investigated. As expected all intracellular viral markers were lower in aviremic as compared to viremic subjects, but in addition both elite and secondary controllers had lower levels of viral unspliced RNA in PBMC as compared to patients on HAART. Ex vivo cultivation of the virus from CD4+ T cells of SC consistently failed in one patient and showed delayed kinetics in the three others. Formal in vitro replication studies of these three viruses showed low to absent growth in two cases and a virus with normal fitness in the third case. T cell responses toward HIV peptides, evaluated in IFN-γ ELISPOT, revealed no significant differences in breadth, magnitude or avidity between SC and all other patient groups. Neither was there a difference in polyfunctionality of CD4+ or CD8+ T cells, as evaluated with intracellular cytokine staining. However, secondary and elite controllers showed higher proliferative responses to Gag and Pol peptides. SC also showed the highest level of autologous neutralizing antibodies. These data suggest that higher T cell proliferative responses and lower replication kinetics might be instrumental in secondary viral control in the absence of treatment. PMID:22666392

  13. Nosocomial infections in human immunodeficiency virus type 1 (HIV-1) infected and AIDS patients: major microorganisms and immunological profile

    PubMed Central

    Panis, C.; Matsuo, T.; Reiche, E.M.V.

    2009-01-01

    Antiretroviral therapy advances have proportioned to AIDS patients a survival increase. At the same time, the permanence of the seropositive people in the nosocomial environment becomes common not only by the adverse reactions caused by this therapy, but also by several opportunistic diseases that take them into and out of hospital environment. During the hospital permanence, the patients expose their impaired immune system to the nosocomial virulent microorganisms, and acquire destructive nosocomial infections that sometimes can be lethal. Among several hospital syndromes described, little is known about infections in immunocompromised patients and how their immune system is able to determine the course of the infection. The objective of this study was to describe the major microorganisms involved in the nosocomial infections of HIV-1 seropositive patients associated with their immunological status. The survey was carried out with the Hospital Infection Control Service records, from University Hospital, Londrina, Paraná, Southern of Brazil, during the period from July 2003 to July 2004. From all the cases studied (n=969), 24 patients (2.5%) had AIDS diagnosis and a half of them was women with the mean of CD4+ T cells counts of 158/mm3. The main topography of the infection was pulmonary (50.0%) and the main isolated microorganisms were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. A major incidence of infection was observed in patients with CD4+ T cells counts lower than 50/mm3. The study of the relationship between the impairment of the immune system and infectious agents could provide a better healthcare of people living with HIV/AIDS and advances into the nosocomial infection control systems. PMID:24031336

  14. Predictors of unprotected sexual intercourse among HIV-infected patients receiving antiretroviral drugs in the Niger Delta Region of Nigeria.

    PubMed

    Ebuenyi, Ikenna Desmond; Ogoina, Dimie; Harry, Tubonye Clement

    2017-08-22

    This study aims to evaluate the predictor of unprotected sexual intercourse among HIV-infected adults receiving antiretroviral therapy (ART) in a tertiary facility in the Niger Delta Region of Nigeria. A cross sectional study was undertaken in a 200 bed tertiary hospital in Bayelsa state, south-south Nigeria. A standardized pre-tested interviewer administered questionnaire was used to collect demographic, clinical and sexual history from consecutive HIV-1 infected adults receiving ART for at least 6 months. Independent predictors of unprotected sexual intercourse (defined as irregular condom use or unprotected sex in previous 6months) were determined using an unconditional logistic regression model. Out of 241 patients studied, 71.8% were females, 48.5% were married, and 20.7% had a sexual partner that is HIV-1 infected. Sixty (24.9%) patients engaged in unprotected sex, 86 (35.7%) used condom consistently and 95 (39.4%) abstained. Female sex, being currently married, age18-35years, partner being HIV-positive and living with sexual partner were significant associated with risky sex. Female sex, age18-35years and being currently married were the only independent predictors of unprotected sex. HIV-infected adults receiving ART in resource limited settings are potential sources of secondary transmission of HIV. Condom use in the prevention of secondary transmission of HIV in study area should target females, young adults and married couples.

  15. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study.

    PubMed

    Dolling, David I; Dunn, David T; Sutherland, Katherine A; Pillay, Deenan; Mbisa, Jean L; Parry, Chris M; Post, Frank A; Sabin, Caroline A; Cane, Patricia A

    2013-10-01

    To determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir. Resistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list. Four hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84-3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience. Viral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented.

  16. Long-Term Efficacy of First Line Antiretroviral Therapy in Indian HIV-1 Infected Patients: A Longitudinal Cohort Study

    PubMed Central

    Neogi, Ujjwal; Heylen, Elsa; Shet, Anita; Chandy, Sara; Shamsunder, Ranjani; Sönnerborg, Anders; Ekstrand, Maria L.

    2013-01-01

    Background Short term efficacy of combination antiretroviral therapy (cART) in resource-constrained settings is comparable to that found in western studies. However, long term data are limited. India has the third largest HIV infected population in the world but the long-term outcome of first line therapy according to the national guidelines has not been evaluated yet. Therefore, we conducted a long-term longitudinal analysis of the efficacy of the national first-line therapy in India from an observational cohort of Indian patients in two different clinical settings. Methodology/Principal Findings A total 323 patients who had been on ART for a median of 23 months and achieved virological suppression <100 copies/ml by their study baseline visit, were included and followed for two years. Blood samples were collected every six months for viral load and CD4 count. Drug resistance genotyping was performed when the viral load was >2000 copies/mL. Adherence and treatment interruptions (>48 h) were assessed via self-report. In the studied patients, the median duration of viral suppression was 44 months; 15.8% of patients showed viral rebound, and 2.8% viral failure. Viral rebound or failure was significantly negatively related to perfect adherence (100% adherence and no treatment interruption >48 hrs). Virological re-suppression in the subsequent visit was observed in three patients without any change in therapy despite the presence of key mutations. Conclusion/Significance Our study reports for the first time, a good long-term response to the first line therapy for a median of nearly four years although a less than perfect adherence increases the risk for treatment failure and subsequent drug resistance development. The empirical findings in this study also indicate the overall success of the Indian ART program in two different settings which likely are representative of other clinics that operate under the national guidelines. PMID:23383185

  17. Renal function monitoring in patients receiving lithium carbonate.

    PubMed

    Gelenberg, A J; Wojcik, J D; Coggins, C H; Rosenbaum, J F; LaBrie, R A

    1981-11-01

    As a screening test for renal function, urine concentration was measured following a 12-hour overnight fast in 54 outpatients taking lithium carbonate and 19 patients receiving antidepressant drugs. A significantly greater percentage of lithium patients failed to achieve a maximum urine concentration of 600 mOsm/kg (63% versus 33% in the antidepressant group, p less than .001). This level, a compromise between the sensitivity and specificity of the test, is viewed as a cutoff point for further testing. It is concluded that urine concentration testing is a feasible first-line screen for renal function among lithium-treated patients. Other preliminary studies include routine urinalysis, serum creatinine determination, and estimated creatinine clearance. Second-line testing includes a repeated dehydration test and administration of DDAVP.

  18. [Critically ill patients with 2009 pandemic influenza A (H1N1) infection in Spain: factors associated with death, April 2009-January 2010].

    PubMed

    Santa-Olalla Peralta, Patricia; Cortes García, Marta; Limia Sánchez, Aurora; Andrés Prado, Josefa; Pachón Del Amo, Isabel; Sierra Moros, Maria José

    2010-01-01

    It is necessary to analyse the severe cases of pandemic influenza infection in order to identify vulnerable populations and adapt prevention and control policies accordingly. We analysed the clinical and epidemiological characteristics and risk factors associated with death in patients with 2009 pandemic influenza A (H1N1) infection hospitalised in intensive care units (ICUs) in Spain and reported from 24 April 2009 to 31 January 2010. As part of the national strategy for surveillance of hospitalized cases with pandemic influenza, cased-based clinical and epidemiological information on all cases admitted to an ICU with 2009 pandemic virus (H1N1) infection was collected nationwide. Of 1,231 cases admitted to ICU, 271 died (case fatality ratio, 22%). The median age was 40 years (range: 0-90). A total of 838 (76.3%) patients had an underlying risk condition, being respiratory disease the most frequently reported (34.1%), followed by morbid obesity (18.8%), in adults. Antiviral treatment was given in 93.1% patients and in 25.6% (n = 231) it was initiated within 48 hours of symptoms onset. In a multivariate analysis, cancer (OR 2.71, 95%CI 1.44 to 5.1), immunodeficiency (OR 2.25, 95%CI 1.29 - 3.92) and morbid obesity (OR 1.79, 95%CI 1.13 to 2.85) were significantly associated with death in adults. The characterization of severe pandemic influenza cases has been crucial in identifying as risk factors of complications and death from influenza the presence of cancer and immunodeficiencies and for the first time, morbid obesity in adults.

  19. Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection--a randomized trial.

    PubMed

    Poordad, Fred; Lawitz, Eric; Reddy, K Rajender; Afdhal, Nezam H; Hézode, Christophe; Zeuzem, Stefan; Lee, Samuel S; Calleja, Jose Luis; Brown, Robert S; Craxi, Antonio; Wedemeyer, Heiner; Nyberg, Lisa; Nelson, David R; Rossaro, Lorenzo; Balart, Luis; Morgan, Timothy R; Bacon, Bruce R; Flamm, Steven L; Kowdley, Kris V; Deng, Weiping; Koury, Kenneth J; Pedicone, Lisa D; Dutko, Frank J; Burroughs, Margaret H; Alves, Katia; Wahl, Janice; Brass, Clifford A; Albrecht, Janice K; Sulkowski, Mark S

    2013-11-01

    Treatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety. Patients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavirin dosage reduction (n = 249) or erythropoietin therapy (n = 251). Rates of SVR were comparable between patients whose anemia was managed by ribavirin dosage reduction (71.5%) vs erythropoietin therapy (70.9%), regardless of the timing of the first intervention to manage anemia or the magnitude of ribavirin dosage reduction. There was a threshold for the effect on rate of SVR: patients who received <50% of the total milligrams of ribavirin assigned by the protocol had a significantly lower rate of SVR (P < .0001) than those who received ≥50%. Among patients who did not develop anemia, the rate of SVR was 40.1%. Eleven thromboembolic adverse events were reported in 9 of 295 patients who received erythropoietin, compared with 1 of 392 patients who did not receive erythropoietin. Reduction of ribavirin dosage can be the primary approach for management of anemia in patients receiving peginterferon, ribavirin, and boceprevir for HCV infection. Reduction in ribavirin dosage throughout the course of triple therapy does not affect rates of SVR. However, it is important that the patient receives at least 50% of the total amount (milligrams) of ribavirin assigned by response-guided therapy. ClinicalTrials.gov number, NCT01023035. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. Shorter telomere length predicts poorer immunological recovery in virologically suppressed HIV-1-infected patients treated with combined antiretroviral therapy.

    PubMed

    Blanco, José-Ramón; Jarrin, Inma; Martinez, Alfredo; Siles, Eva; Larrayoz, Ignacio M; Cañuelo, Ana; Gutierrez, Félix; Gonzalez-Garcia, Juan; Vidal, Francesc; Moreno, Santiago

    2015-01-01

    Successful combined antiretroviral therapy (cART) does not always result in complete CD4 T-cell recovery despite the effective control of HIV replication. Because telomere dysregulation can lead to an abnormal cell proliferation, we hypothesized that the lack of CD4 recovery may be related to telomere defects; We thus evaluated the association between telomere length (TL) and CD4 T-cell recovery 48 weeks after cART initiation in virologically suppressed patients, and its possible relationship to oxidative stress (OS) and nitrosative stress (NOx) markers. We studied HIV-infected patients on stable cART who achieved a viral load <50 copies per milliliter after 48 weeks of their first cART. Leukocyte TL was measured and categorized into tertiles. We calculated mean increases in CD4 T-cell at 48 weeks from cART initiation and used multivariate linear regression models to estimate differences in mean increases according to tertiles of TL. One hundred thirty-two patients, 86% male, 81% <50 years at cART initiation were studied. Mean increases in CD4 were greater in patients with long TL than in those with medium and short TLs (P = 0.007). After adjustment for sex, age, CD4 T-cell counts, viral load, and hepatitis C infection at cART initiation, differences in mean CD4 T-cell count increases according to TL remained statistically significant (P = 0.02). Additional adjustment for NOx and OS did not change the results. A lower immunological response despite a successful virological response is associated with a shorter TL. The effect is not related to NOx or OS.

  1. A Cost-Utility Analysis of Different Antiviral Medicine Regimens in Patients With Chronic Hepatitis C Virus Genotype 1 Infection

    PubMed Central

    Alavian, Seyed Moayed; Nikfar, Shekoufeh; Kebriaeezadeh, Abbas; Lotfi, Farhad; Sanati, Ehsan; Rezaei Hemami, Mohsen; Keshavarz, Khosro

    2016-01-01

    Background Despite the introduction of new drug regimens with high effectiveness for the hepatitis C virus (HCV) patients, especially in HCV genotype 1, no cost-effectiveness study on the selection of the superior drug strategy in Iran has been conducted yet. Objectives This study is aimed to assess the cost-effectiveness of the three drug regimens of pegylated interferon and ribavirin (PR), sofosbuvir (SOF) + PR and ledipasvir and sofosbuvir (LDV/SOF) in patients with HCV genotype 1 in Iran in the year 2014. Methods A Markov micro-simulation model was used to evaluate the cost-effectiveness of the three drug strategies for a cohort of 10000 patients. Quality-adjusted life-years (QALYs) were extracted from published studies. Cost data was estimated through the review of medical records and obtaining experts opinion. Results The results showed that the SOF + PR drug compared with PR had a lower cost and was more effective, but compared with the LDV/SOF, in spite of its lower cost, it was less efficient. The QALY values obtained for PR, SOF + PR and LDV/SOF, respectively, were 10.98, 12.08 and 12.28 and their costs were $ 41,741, $ 7,676 and $ 46,993. Moreover, the results obtained from acceptability curves showed that SOF + PR were the most cost-effective treatment for thresholds below $ 45,270 PPP. Conclusions The use of SOF + PR regimen or LDV/SOF can significantly reduce the incidence of complications associated with the disease. For example, short and long-term outcomes are better than the current drug regimens for HCV genotype 1 patients in all stages of the disease. PMID:28203449

  2. Low frequency of genotypic resistance in HIV-1-infected patients failing an atazanavir-containing regimen: a clinical cohort study

    PubMed Central

    Dolling, David I.; Dunn, David T.; Sutherland, Katherine A.; Pillay, Deenan; Mbisa, Jean L.; Parry, Chris M.; Post, Frank A.; Sabin, Caroline A.; Cane, Patricia A.; Aitken, Celia; Asboe, David; Webster, Daniel; Cane, Patricia; Castro, Hannah; Dunn, David; Dolling, David; Chadwick, David; Churchill, Duncan; Clark, Duncan; Collins, Simon; Delpech, Valerie; Geretti, Anna Maria; Goldberg, David; Hale, Antony; Hué, Stéphane; Kaye, Steve; Kellam, Paul; Lazarus, Linda; Leigh-Brown, Andrew; Mackie, Nicola; Orkin, Chloe; Rice, Philip; Pillay, Deenan; Phillips, Andrew; Sabin, Caroline; Smit, Erasmus; Templeton, Kate; Tilston, Peter; Tong, William; Williams, Ian; Zhang, Hongyi; Zuckerman, Mark; Greatorex, Jane; Wildfire, Adrian; O'Shea, Siobhan; Mullen, Jane; Mbisa, Tamyo; Cox, Alison; Tandy, Richard; Hale, Tony; Fawcett, Tracy; Hopkins, Mark; Ashton, Lynn; Booth, Claire; Garcia-Diaz, Ana; Shepherd, Jill; Schmid, Matthias L.; Payne, Brendan; Hay, Phillip; Rice, Phillip; Paynter, Mary; Bibby, David; Kirk, Stuart; MacLean, Alasdair; Gunson, Rory; Coughlin, Kate; Fearnhill, Esther; Fradette, Lorraine; Porter, Kholoud; Ainsworth, Jonathan; Anderson, Jane; Babiker, Abdel; Fisher, Martin; Gazzard, Brian; Gilson, Richard; Gompels, Mark; Hill, Teresa; Johnson, Margaret; Kegg, Stephen; Leen, Clifford; Nelson, Mark; Palfreeman, Adrian; Post, Frank; Sachikonye, Memory; Schwenk, Achim; Walsh, John; Huntington, Susie; Jose, Sophie; Thornton, Alicia; Glabay, Adam; Orkin, C.; Garrett, N.; Lynch, J.; Hand, J.; de Souza, C.; Fisher, M.; Perry, N.; Tilbury, S.; Gazzard, B.; Nelson, M.; Waxman, M.; Asboe, D.; Mandalia, S.; Delpech, V.; Anderson, J.; Munshi, S.; Korat, H.; Welch, J.; Poulton, M.; MacDonald, C.; Gleisner, Z.; Campbell, L.; Gilson, R.; Brima, N.; Williams, I.; Schwenk, A.; Ainsworth, J.; Wood, C.; Miller, S.; Johnson, M.; Youle, M.; Lampe, F.; Smith, C.; Grabowska, H.; Chaloner, C.; Puradiredja, D.; Walsh, J.; Weber, J.; Ramzan, F.; Mackie, N.; Winston, A.; Leen, C.; Wilson, A.; Allan, S.; Palfreeman, A.; Moore, A.; Wakeman, K.

    2013-01-01

    Objectives To determine protease mutations that develop at viral failure for protease inhibitor (PI)-naive patients on a regimen containing the PI atazanavir. Methods Resistance tests on patients failing atazanavir, conducted as part of routine clinical care in a multicentre observational study, were randomly matched by subtype to resistance tests from PI-naive controls to account for natural polymorphisms. Mutations from the consensus B sequence across the protease region were analysed for association and defined using the IAS-USA 2011 classification list. Results Four hundred and five of 2528 (16%) patients failed therapy containing atazanavir as a first PI over a median (IQR) follow-up of 1.76 (0.84–3.15) years and 322 resistance tests were available for analysis. Recognized major atazanavir mutations were found in six atazanavir-experienced patients (P < 0.001), including I50L and N88S. The minor mutations most strongly associated with atazanavir experience were M36I, M46I, F53L, A71V, V82T and I85V (P < 0.05). Multiple novel mutations, I15S, L19T, K43T, L63P/V, K70Q, V77I and L89I/T/V, were also associated with atazanavir experience. Conclusions Viral failure on atazanavir-containing regimens was not common and major resistance mutations were rare, suggesting that adherence may be a major contributor to viral failure. Novel mutations were described that have not been previously documented. PMID:23711895

  3. Clinical analysis of cholangiocarcinoma patients receiving adjuvant radiotherapy

    PubMed Central

    Nantajit, Danupon; Trirussapanich, Pornwaree; Rojwatkarnjana, Sunanta; Soonklang, Kamonwan; Pattaranutraporn, Poompis; Laebua, Kanyanee; Chamchod, Sasikarn

    2016-01-01

    Cholangiocarcinoma (CCA) or bile duct cancer is a rare cancer type in developed countries, while its prevalence is increased in southeast Asia, affecting ~33.4 men and ~12.3 women per 100,000 individuals. CCA is one of the most lethal types of cancer. Neo-adjuvant and adjuvant therapies have been shown to have limited efficacy in improving the overall prognosis of patients. Radiotherapy has been reported to prolong the survival times of patients with certain characteristics. The present study retrospectively evaluated the medical records and follow-up data from 27 CCA patients who received radiotherapy at Chulabhorn Hospital (Bangkok, Thailand) between 2008 and 2014. A total of 14 patients underwent surgery followed by adjuvant chemoradiotherapy. Of the 27 CCA patients, 14 had intrahepatic CCA, 2 had extrahepatic CCA and 11 had hilar CCA. The 2-year survival rate was 40.7%. Tumor resectability, clinical symptoms and the Eastern Cooperative Oncology Group performance status score were found to be indicative of patient prognosis. In addition, the planning target volume and biologically effective radiotherapy dose were of prognostic value; however, initial treatment response was ambiguous in predicting survival time. The findings of the present study suggested that the currently used radiotherapy protocols for CCA may require modification to improve their efficacy. PMID:28105359

  4. Selective serotonin reuptake inhibitor drug interactions in patients receiving statins.

    PubMed

    Andrade, Chittaranjan

    2014-02-01

    Elderly patients commonly receive statin drugs for the primary or secondary prevention of cardiovascular and cerebrovascular events. Elderly patients also commonly receive antidepressant drugs, usually selective serotonin reuptake inhibitors (SSRIs), for the treatment of depression, anxiety, or other conditions. SSRIs are associated with many pharmacokinetic drug interactions related to the inhibition of the cytochrome P450 (CYP) metabolic pathways. There is concern that drugs that inhibit statin metabolism can trigger statin adverse effects, especially myopathy (which can be potentially serious, if rhabdomyolysis occurs). However, a detailed literature review of statin metabolism and of SSRI effects on CYP enzymes suggests that escitalopram, citalopram, and paroxetine are almost certain to be safe with all statins, and rosuvastatin, pitavastatin, and pravastatin are almost certain to be safe with all SSRIs. Even though other SSRI-statin combinations may theoretically be associated with risks, the magnitude of the pharmacokinetic interaction is likely to be below the threshold for clinical significance. Risk, if at all, lies in combining fluvoxamine with atorvastatin, simvastatin, or lovastatin, and even this risk can be minimized by using lower statin doses and monitoring the patient.

  5. Metabolic issues in schizophrenic patients receiving antipsychotic treatment.

    PubMed

    Gupta, Aditi; Dadheech, Gora; Yadav, Dharamveer; Sharma, Praveen; Gautam, Shiv

    2014-04-01

    Schizophrenia is a psychotic disorder with a complex pathophysiology and requires treatment that includes long term administration of antipsychotics that is said to be associated with metabolic syndrome. This study was designed to evaluate the impact of seven different antipsychotics prescribed to schizophrenic patients, on development of metabolic syndrome in the patients. A total of 210 patients with schizophrenia (30 patients in each drug therapy group) were recruited according to ICD-10 criteria and were assigned to receive the drug for 16 weeks. Measurement of anthropometric (body weight, waist circumference, blood pressure) and biochemical parameters (glucose, insulin, HOMA-IR, triglycerides, LDL, HDL) was done and the patients were subjected to ATP-III defined criteria for metabolic syndrome. Patients undergoing treatment with olanzapine were more prone to metabolic syndrome as the drug induces weight gain after 16 weeks of treatment. It also induces dyslipidemia (P < 0.001) and hyperglycemia (P < 0.01). Clozapine was found to be second most potent drug in inducing metabolic syndrome as the weight in clozapine treated patients increased after 16 weeks, along with a significant increase in glycemic (P < 0.001) and lipid parameters (P < 0.01). Aripriazole and amisulphride are comparatively safer drugs as their role in inducing metabolic abnormalities in schizophrenic patients was insignificant, although the impact of long term administration of these drugs needs to be explored. It is clear from the study that antipsychotic treatment induces metabolic syndrome so, it becomes important that the metabolic and cardiovascular risk factors should be surveillance regularly in schizophrenic patients undergoing antipsychotic treatment.

  6. Characteristics and health behaviors of diabetic patients receiving influenza vaccination.

    PubMed

    Achtymichuk, Karly A; Johnson, Jeffrey A; Al Sayah, Fatima; Eurich, Dean T

    2015-07-09

    Epidemiological research has posited a 'healthy user' bias in patients receiving influenza vaccination; thus we sought to evaluate potential healthy-user attributes and their associations with influenza vaccination. Between 2011 and 2013, adults with type 2 diabetes were enrolled in a prospective cohort in Alberta, Canada. Information collected included sociodemographics, diabetes-related data (e.g., duration, complications), health behaviors (e.g., smoking status), functional health status, and satisfaction with healthcare. Data were collected by a mailed, self-administered survey. Multivariable logistic regression analyses were used to identify potential healthy-user attributes independently associated with influenza vaccination. From a cohort of 2040 patients, 1287 (63%) reported receiving the influenza vaccine in the previous year. Average age of the cohort was 64 years (standard deviation 11) and 55% were male. In multivariable analysis, attributes independently associated with influenza vaccination included receiving preventive medications: aspirin (64% vs 44%; adjusted odds ratio, aOR 1.65, 95% CI 1.34-2.04); blood pressure medications (76% vs 56%; aOR 1.36, 95% CI 1.07-1.71); and cholesterol-lowering medications (74% vs 53%; aOR 1.50, 95% CI 1.19-1.89), as well as having a healthcare professional check feet for lesions (47% vs 31%; aOR 1.39, 95% CI 1.12-1.74). Additional covariates independently associated with influenza vaccination included: age over 65 years, respiratory disease, the number of additional comorbidities, and higher ratings of healthcare experience. Vaccinated diabetic patients exhibit many postulated attributes of 'healthy users', which has implications for the interpretation of epidemiological studies of influenza vaccine effectiveness, as well as targeting future vaccination campaigns. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Moving from viral suppression to comprehensive patient-centered care: the high prevalence of comorbid conditions and health risk factors in HIV-1-infected patients in Australia.

    PubMed

    Broom, Jennifer; Sowden, David; Williams, Merran; Taing, Kuong; Morwood, Karen; McGill, Karen

    2012-01-01

    HIV clinicians today need to move from focusing on viral suppression to a chronic disease model in which comorbid conditions and risk factors are comprehensively identified and addressed to reduce rates of serious non-AIDS-related morbidity and mortality. This study aimed to determine the prevalence of comorbid conditions in an Australian HIV-positive population. Of 180 patients included, there was a median CD4 count of 0.520 cells/mm(3). The majority (88%) of patients were currently receiving highly active antiretroviral therapy (HAART). There were high rates of failure to attend clinical appointments (30%), current smoking (42%), hypertension (16%), and dyslipidemia (17%). Significant rates of dipstick-positive proteinuria (16%) and elevated blood glucose (15%) were recorded. Risk factors were commonly not addressed by the treating clinician. There is an urgent need to systematize detection and management of high-prevalence comorbid conditions to prevent premature mortality associated with serious non-AIDS events.

  8. Dynamics of PBMC gene expression in hepatitis C virus genotype 1-infected patients during combined peginterferon/ribavirin therapy

    PubMed Central

    Lu, Ming-Ying; Huang, Ching-I; Hsieh, Ming-Yen; Hsieh, Tusty-Juan; Hsi, Edward; Tsai, Pei-Chien; Tsai, Yi-Shan; Lin, Ching-Chih; Hsieh, Meng-Hsuan; Liang, Po-Cheng; Lin, Yi-Hung; Hou, Nai-Jen; Yeh, Ming-Lun; Huang, Chung-Feng; Lin, Zu-Yau; Chen, Shinn-Cherng; Huang, Jee-Fu; Chuang, Wan-Long; Dai, Chia-Yen; Yu, Ming-Lung

    2016-01-01

    Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment. A complete early virologic response (cEVR) was defined as negative HCV RNA at treatment week 12. Forty-three differentially expressed genes identified by Affymetrix microarray were validated by quantitative polymerase chain reaction. Thirteen genes at week 1 and 24 genes at week 4 were upregulated in the SVR group compared with the non-SVR group. We selected 8 target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3, and DDX60) at week 1 as the major components of the predictive model. This predictive model reliably stratified the responders and non-responders at week 1 (AUC = 0.89, p = 0.007 for SVR; AUC = 0.95, p = 0.003 for cEVR), especially among patients carrying the IL28B rs8099917 TT genotype (AUC = 0.89, p = 0.02 for SVR; AUC = 1.0, p = 0.008 for cEVR). The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype. PMID:27542257

  9. Clinical Features Associated with HIV-1 Infection in Adult Patients Diagnosed with Tuberculosis in Djibouti, Horn of Africa

    DTIC Science & Technology

    1993-01-01

    WITH TUBERCULOSIS IN DJIBOUTI, HORN OF AFRICA - By G.R. Rodier , J.P. S~vre, G. Binson, G.C. Gray, Said-Salah, and P. Gravier U.S. NAVAL MEDICAL RESEARCH...WU- 3M46310SH29.AA.335 6. AUTHOR(S) Rodier , G.R., Sbvre, J.P., Binson, G., Gray, G.C., Said-Salab, and Gravier, P. 7. PERFORMING ORGANIZATION NAME(S...with HIV for this study. One hundred and G. R. Rodier ’.2, J. P. Svreie3’, G. Binson 3.4, G. C. six of the 1844 TB patients (5.7%) had antibodies

  10. [Adult T-cell leukemia/lymphoma in HTLV-1 infected patients: report of two cases in Colombia].

    PubMed

    Medina, Edwin Abraham; Orduz, Rocío; Morales, Olga Lucía; Martínez, Óscar; Baldión, Margarita; Isaza, Mario Arturo

    2013-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a malignant neoplasia of mature CD4+ T lymphocytes,resulting from infection with human T-lymphotropic virus type 1 (HTLV-1), with several systemic and cutaneous manifestations. We present two cases of adult T-cell leukemia/lymphoma, in patients from the Colombian Southwestern region, whose diagnoses were confirmed by histology, immunohistochemistry, flow cytometry, ELISA and Western blot tests. We also discuss about the virus and how to make this diagnosis in countries like Colombia.

  11. Fatigue experienced by patients receiving maintenance dialysis in hemodialysis units.

    PubMed

    Letchmi, Santhna; Das, Srijit; Halim, Hasliza; Zakariah, Farid Azizul; Hassan, Hamidah; Mat, Samsiah; Packiavathy, Ruth

    2011-03-01

    The fatigue that is observed in patients who are undergoing dialysis is usually associated with an impaired quality of life. The present cross-sectional study was conducted from January to April 2009 in three hemodialysis units in Kuala Lumpur, Malaysia. In this study, the Multidimensional Fatigue Inventory and Depression Anxiety and Stress Score 21 were used to determine the level of fatigue, depression, anxiety, and stress of patients who were undergoing dialysis. The data were obtained from a calculated sample of 116 and a total of 103 respondents participated in the study. A total of 56 (54.4%) and 47 (45.6%) respondents experienced a high level and a low level of fatigue, respectively. There was a significant relationship between the duration of treatment and the level of fatigue. The respondents who had been receiving treatment for > 2 years experienced more fatigue, compared to the respondents who had been undergoing hemodialysis for > 2 years. There was a significant difference in relation to the age of the participants regarding the level of fatigue. No significant relationship between the sex of the participants, anemia, depression, anxiety, stress, and the level of fatigue was observed. Special attention needs to be paid to both the younger and older adults who are receiving treatment. In addition, proper planning is needed for the patients regarding their daily activities in order to reduce fatigue. Nurses who work in hemodialysis units are recommended to provide exercise classes or group therapy in order to boost the energy levels among patients who are undergoing dialysis. Health professionals should provide appropriate treatment for patients who are experiencing fatigue in order to prevent any other complications that could arise.

  12. Churg-Strauss syndrome (CSS) in a patient receiving pranlukast.

    PubMed

    Kobayashi, Shigeto; Ishizuka, Shyugo; Tamura, Naoto; Takaya, Makiyo; Kaneda, Kazuhiko; Hashimoto, Hiroshi

    2003-12-01

    Pranlukast is a cysteinyl leukotriene receptor I antagonist (LTRAs) approved for treatment of asthma in Japan since 1995. Compared to other LTRAs, such as zafilukast and montelukast, only few cases with Churg-Strauss syndrome (CSS) have been reported in association with treatment with pranlukast. We describe a 17-year-old Japanese male patient who developed CSS with a 13 month history of mild asthma receiving pranlukast for 11 months without systemic and/or inhaled corticosteroid administration prior to development of CSS. From the aspect of temporal relationship between treatment with pranlukast and development of CSS, a direct induction of CSS by pranlukast is suggested in our case.

  13. Dynamics of HIV-1 mRNA expression in patients with long-term nonprogressive HIV-1 infection.

    PubMed Central

    Comar, M; Simonelli, C; Zanussi, S; Paoli, P; Vaccher, E; Tirelli, U; Giacca, M

    1997-01-01

    A large number of evidences indicate that progression of HIV disease is driven by an increase in viral burden. It is still unclear, however, to what extent this is contributed by the dysregulation of the molecular mechanisms governing virus gene expression at the transcriptional or posttranscriptional levels. To address this issue, several quantitative virologic parameters (including provirus transcriptional activity and splicing pattern) were analyzed in individuals with nonprogressive HIV infection and compared with those of a matched group of progressor patients. Exact quantification was achieved by a competitive PCR procedure using a multicompetitor template. Nonprogressors were characterized by striking differences in the levels of viremia, provirus copy number, and overall levels of all viral mRNA classes in peripheral blood mononuclear cells. Additionally, the transcriptional activity of the proviral DNA in these patients was mainly engaged in the production of multiprocessed transcripts, with a pattern resembling the early phases of the experimental infection. Taken together, these results show that both viral load and provirus transcription pattern are remarkably different in infected individuals nonprogressing toward overt disease, and further support the notion that disease progression is accompanied by a change in the kinetics of HIV gene expression. PMID:9259589

  14. Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of HIV-1-infected patients with cutaneous pseudolymphoma.

    PubMed Central

    Bachelez, H; Hadida, F; Parizot, C; Flageul, B; Kemula, M; Dubertret, L; Debree, P; Gorochov, G

    1998-01-01

    A massive infiltration of the skin by activated CD8+ T lymphocytes involving both the dermis and the epidermis has been found in HIV-1-infected patients presenting with a chronic skin rash. We characterized the T cell receptor (TCR) BV-BJ junctional diversity of the skin-infiltrating lymphocytes (SILs) in four patients. The SILs expressed a limited set of TCRBV gene segments. Complementarity determining region 3 length analysis further emphasized their oligoclonality, suggesting that antigen stimulation might be responsible for the cutaneous T cell expansion. Furthermore, independent skin biopsies obtained from the same individual were shown to harbor distinct T cell repertoires, possibly reflecting the spatial heterogeneity of the antigenic stimuli. The CD8+ cytotoxic T lymphocyte (CTL) lines isolated from the skin rash in one patient exhibited a specific, class I MHC-restricted cytotoxic activity against HIV-1 Gag- and Pol-expressing target cells, whereas CTL lines derived from the skin lesions of a second patient were shown to be predominantly Env-specific. Taken together, these data demonstrate the infiltration of HIV-specific CTLs in the skin of HIV-infected patients, and suggest that in addition to their known role in controlling the retroviral infection, these CTLs may also be involved in the pathogenesis of cutaneous inflammatory disorders occurring during the course of HIV infection. PMID:9616222

  15. Epidemiology of Mycoplasma acquisition in male HIV-1 infected patients: a multistage cross-sectional survey in Jiangsu, China.

    PubMed

    Chen, L-S; Wu, J-R; Wang, B; Yang, T; Yuan, R; Zhao, Y-Y; Xu, J-S; Guo, H-X; Huan, X-P

    2015-11-01

    Mycoplasma infections are most frequently associated with disease in the urogenital or respiratory tracts and, in most cases, mycoplasmas infect the host persistently. In HIV-infected individuals the prevalence and role of genital mycoplasmas has not been well studied. To investigate the six species of Mycoplasma and the risk factors for infection in Jiangsu province, first-void urine and venous blood samples were collected and epidemiological questionnaires were administered after informed consent. A total of 1541 HIV/AIDS patients were recruited in this study. The overall infection rates of six Mycoplasma species were: Ureaplasma urealyticum (26·7%), Mycoplasma hominis (25·3%), M. fermentans (5·1%), M. genitalium (20·1%), M. penetrans (1·6%) and M. pirum (15·4%). The Mycoplasma infection rate in the unmarried group was lower than that of the married, divorced and widowed groups [adjusted odds ratio (aOR) 1·432, 95% confidence interval (CI) 1·077-1·904, P < 0·05]. The patients who refused highly active antiretroviral therapy (HAART) had a much higher risk of Mucoplasma infection (aOR 1·357, 95% CI 1·097-1·679, P < 0·05). Otherwise, a high CD4+ T cell count was a protective factor against Mycoplasma infection (aOR 0·576, 95% CI 0·460-0·719, P < 0·05). Further research will be required to confirm a causal relationship and to identify risk factors for Mycoplasma infection in HIV/AIDS populations.

  16. Dental procedures in patients receiving oral anticoagulation therapy.

    PubMed

    Saour, J N; Ali, H A; Mammo, L A; Sieck, J O

    1994-05-01

    Over a 10-year period a uniform management plan for patients receiving long term oral anticoagulation therapy for prosthetic heart valves and needing dental procedures was instituted. Those undergoing dental extraction or gum hygiene in the presence of gross gum pathology (Group A) had their oral anticoagulation discontinued two days prior to the procedure which was carried out only if the INR was 1.5 or less on the day of the procedure. Patients who needed dental fillings or gum hygiene in the absence of gross gum pathology (Group B) continued their anticoagulation therapy and had these procedures completed provided the INR was 3.0 or less. The main outcome measured were valve thrombosis, thromboembolism and excessive bleeding requiring hospitalization and/or blood transfusion. In Group A, 240 procedures were carried out; 212 dental extractions and 28 dental hygiene in the presence of gross gum pathology. They had a brief period of under-anticoagulation (3-7 days) to an INR of 1.5 or less. In Group B, 156 procedures were performed. No patient developed valve thrombosis or thromboembolism. Two patients, both in Group A needed hospitalization for observation but no blood transfusion. This management plan was easy to implement. Patients needed one extra visit to the anticoagulation clinic within one week of the procedure. It was both safe and effective.

  17. Receiving difficult news. Views of patients in an inpatient setting.

    PubMed

    Cleary, Michelle; Hunt, Glenn E; Escott, Phil; Walter, Garry

    2010-06-01

    For this quantitative study, a cross-sectional design was used to assess patients' ratings regarding receiving difficult news pertaining to their psychiatric illness, such as deleterious lifestyle consequences and lifelong medications. One hundred inpatients were interviewed and completed the survey. Nearly all agreed they had a legal or moral right to information about their diagnosis, and most agreed they should be told their diagnosis. The majority believed the doctor was the best person to tell them their diagnosis, and more than half indicated that not providing a diagnosis was more concerning than be ing told. Approximately two fifths of patients indicated they would prefer to hear difficult news in the presence of key family members or over several sessions, and more than three quarters thought providing hope, regardless of circumstances, was important. The highest response rates were for staff to provide accurate and reliable information, be honest and answer patients' questions, and inform patients of their treatment options and side effects. These results indicate the importance of communicating accurate and timely information to patients in an empathic and understanding manner.

  18. Trajectories of personal control in cancer patients receiving psychological care.

    PubMed

    Zhu, Lei; Schroevers, Maya J; van der Lee, Marije; Garssen, Bert; Stewart, Roy E; Sanderman, Robbert; Ranchor, Adelita V

    2015-05-01

    This study aimed to (1) identify subgroups of cancer patients with distinct personal control trajectories during psychological care, (2) examine whether socio-demographic, clinical, and psychological care characteristics could distinguish trajectories, and (3) examine differential patterns of psychological symptoms between trajectories. This naturalistic study focused on 241 cancer patients receiving psychological care at psycho-oncology institutions. Data were collected before the initiation of psychological care, and 3 and 9 months thereafter. Latent class growth analysis was applied to identify personal control trajectories. Three personal control trajectories were identified: enduring improvement (41%), temporary improvement (50%), and deterioration (9%). Education and baseline physical symptoms distinguished these trajectories. In the whole group, improvements in personal control were associated with improvements in psychological symptoms. Patients at distinct trajectories reported different levels of psychological symptoms, but did not differ in their courses of psychological symptoms. Patients in the enduring and temporary control improvement groups experienced significant psychological symptoms reductions over time, whereas patients in the control deterioration group maintained high psychological symptoms. Improvements in personal control seem to depend on initial control level: those who start with the highest control levels show subsequent improvements, whereas those with the lowest control levels show subsequent deterioration. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Validating Appetite Assessment Tools among Patients Receiving Hemodialysis

    PubMed Central

    Molfino, Alessio; Kaysen, George A.; Chertow, Glenn M.; Doyle, Julie; Delgado, Cynthia; Dwyer, Tjien; Laviano, Alessandro; Fanelli, Filippo Rossi; Johansen, Kirsten L.

    2016-01-01

    Objective To test the performance of appetite assessment tools among patients receiving hemodialysis. Design Cross-sectional. Setting Seven dialysis facilities in Northern California. Subjects 221 patients receiving hemodialysis. Intervention We assessed five appetite assessment tools [self-assessment of appetite, subjective assessment of appetite, visual analogue scale (VAS), Functional Assessment of Anorexia/Cachexia Therapy (FAACT) score and the Anorexia Questionnaire (AQ)]. Main outcome measures Reported food intake, normalized protein catabolic rate (nPCR), and change in body weight were used as criterion measures, and we assessed associations among the appetite tools and biomarkers associated with nutrition and inflammation. Patients were asked to report their appetite and the percentage of food eaten (from 0% to 100%) during the last meal compared to usual intake. Results Fifty-eight (26%) patients reported food intake ≤50% (defined as poor appetite). The prevalence of anorexia was 12% by self-assessment of appetite, 6% by subjective assessment of appetite, 24% by VAS, 17% by FAACT score, and 12% by AQ. All tools were significantly associated with food intake ≤50% (p<0.001), except self-assessment of appetite. The FAACT score and the VAS had the strongest association with food intake ≤50% (c-statistic 0.80 and 0.76). Patients with food intake ≤50% reported weight loss more frequently than patients without low intake (36% vs 22%) and weight gain less frequently (19% vs 35%; p=0.03). nPCR was lower among anorexic patients based on the VAS (1.1 ± 0.3 vs 1.2 ± 0.3, p=0.03). Ln IL-6 correlated inversely with food intake (p=0.03), but neither IL-6 nor CRP correlated with any of the appetite tools. Furthermore, only the self-assessment of appetite was significantly associated with serum albumin (p=0.02), prealbumin (p=0.02) and adiponectin concentrations (p=0.03). Conclusions Alternative appetite assessment tools yielded widely different estimates of the

  20. Simeprevir with pegylated interferon alfa 2a or 2b plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-2): a randomised, double-blind, placebo-controlled phase 3 trial.

    PubMed

    Manns, Michael; Marcellin, Patrick; Poordad, Fred; de Araujo, Evaldo Stanislau Affonso; Buti, Maria; Horsmans, Yves; Janczewska, Ewa; Villamil, Federico; Scott, Jane; Peeters, Monika; Lenz, Oliver; Ouwerkerk-Mahadevan, Sivi; De La Rosa, Guy; Kalmeijer, Ronald; Sinha, Rekha; Beumont-Mauviel, Maria

    2014-08-02

    Pegylated interferon (peginterferon) alfa 2a or 2b plus ribavirin regimens were the standard of care in patients with hepatitis C virus (HCV) infection, but the sustained virological response can be suboptimum in patients with HCV genotype 1 infection. The efficacy, safety, and tolerability of the combination of simeprevir, a one-pill, once-daily, oral HCV NS3/4A protease inhibitor versus placebo, plus peginterferon alfa 2a or 2b plus ribavirin was assessed in treatment-naive patients with HCV genotype 1 infection. In the QUEST-2, phase 3 study, done at 76 sites in 14 countries (Europe, and North and South Americas), patients with confirmed chronic HCV genotype 1 infection and no history of HCV treatment were randomly assigned with a computer-generated allocation sequence in a ratio of 2:1 and stratified by HCV genotype 1 subtype and host IL28B genotype to receive simeprevir (150 mg once daily, orally), peginterferon alfa 2a (180 μg once weekly, subcutaneous injection) or 2b (according to bodyweight; 50 μg, 80 μg, 100 μg, 120 μg, or 150 μg once weekly, subcutaneous injection), plus ribavirin (1000-1200 mg/day or 800-1400 mg/day, orally; simeprevir group) or placebo (once daily, orally), peginterferon alfa 2a or 2b, plus ribavirin (placebo group) for 12 weeks, followed by just peginterferon alfa 2a or 2b plus ribavirin. Total treatment duration was 24 weeks or 48 weeks (simeprevir group) based on criteria for response-guided therapy (ie, HCV RNA <25 IU/mL undetectable or detectable at week 4 and undetectable week 12) or 48 weeks (placebo). Patients, study personnel, and the sponsor were masked to treatment assignment. The primary efficacy endpoint was sustained virological response at 12 weeks after the planned end of treatment (SVR12). Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01290679. Results from the primary (SVR12, week 60) analysis are presented. 209 (81%) of 257 patients in the simeprevir group and

  1. How health information is received by diabetic patients?

    PubMed Central

    Zare-Farashbandi, Firoozeh; Lalazaryan, Anasik; Rahimi, Alireza; Zadeh, Akbar Hassan

    2015-01-01

    Background: Knowledge of correct information-seeking behavior by the patients can provide health specialists and health information specialists with valuable information in improving health care. This study aimed to investigate the passive receipt and active seeking of health information by diabetic patients. Materials and Methods: A survey method was used in this research on 6426 diabetic patients of whom 362 patients were selected by a no percentage stratified random sampling. The Longo information-seeking behavior questionnaire was used to collect data and they were analyzed by SPSS 20 software. Results: The most common information source by diabetic patients was practitioners (3.12). The minimum usage among the information sources were from charity organizations and emergency phone lines with a usage of close to zero. The amount of health information gained passively from each source has the lowest average of 4.18 and usage of this information in making health decision has the highest average score of 5.83. Analysis of the data related to active seeking of information showed that knowledge of available medical information from each source has the lowest average score of 3.95 and ability in using the acquired information for making medical decisions has the highest average score of 5.28. The paired t-test showed that differences between passive information receipt (41.68) and active information seeking (39.20) considered as statistically significant (P < 0.001). Conclusion: Because diabetic patients are more passive information receivers than active information seekers, the health information must be distributed by passive means to these patients. In addition, information-seeking behavior during different time periods should be investigated; to identify more effective distribution of health information. PMID:26261828

  2. Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope

    PubMed Central

    Penn-Nicholson, Adam; Han, Dong P.; Kim, Soon J.; Park, Hanna; Ansari, Rais; Montefiori, David C.; Cho, Michael W.

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we generated five soluble glutathione S-transferase fusion proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino acids of gp41 ectodomain from M group consensus envelope sequence. Antibody responses in HIV-1-infected patients were evaluated using these proteins and overlapping peptides. We found (i) antibody responses against different regions of gp41 varied tremendously among individual patients, (ii) patients with stronger antibody responses against membrane-proximal external region exhibit broader and more potent neutralizing activity, and (iii) several patients mounted antibodies against epitopes that are near, or overlap with, those targeted by 2F5 or 4E10. These soluble gp41 fusion proteins could be an important source of antigens for future vaccine development efforts. PMID:18068750

  3. Assessment of antibody responses against gp41 in HIV-1-infected patients using soluble gp41 fusion proteins and peptides derived from M group consensus envelope

    SciTech Connect

    Penn-Nicholson, Adam; Han, Dong P.; Kim, Soon J.; Park, Hanna; Ansari, Rais; Montefiori, David C.; Cho, Michael W.

    2008-03-15

    Human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 is targeted by broadly-reactive neutralizing antibodies 2F5 and 4E10, making it an attractive target for vaccine development. To better assess immunogenic properties of gp41, we generated five soluble glutathione S-transferase fusion proteins encompassing C-terminal 30, 64, 100, 142, or 172 (full-length) amino acids of gp41 ectodomain from M group consensus envelope sequence. Antibody responses in HIV-1-infected patients were evaluated using these proteins and overlapping peptides. We found (i) antibody responses against different regions of gp41 varied tremendously among individual patients, (ii) patients with stronger antibody responses against membrane-proximal external region exhibit broader and more potent neutralizing activity, and (iii) several patients mounted antibodies against epitopes that are near, or overlap with, those targeted by 2F5 or 4E10. These soluble gp41 fusion proteins could be an important source of antigens for future vaccine development efforts.

  4. Online social support received by patients with cancer.

    PubMed

    Yli-Uotila, Tiina; Rantanen, Anja; Suominen, Tarja

    2014-03-01

    Patient education in the public healthcare system does not necessarily meet the needs of patients with cancer. Because of this, they may turn to the Internet, or they are guided to electronic sources of social support. The purposes of this study were to describe what kind of social support patients with cancer receive from the Internet and its meaning for them. The data were collected using an online survey that consisted of open-ended questions based on a theory of online social support. The data were analyzed using an inductive content analysis. Online social support consisted of three categories: disease-related information from reliable sources, supportive interaction enhancing positive emotions, and practical tips for daily life with cancer. Three major categories related to the meaning of online social support were identified: peers helping make life easier, empowerment, and inadequate support. The findings can be utilized in tailoring educational interventions for patients with cancer. In the future, the long-lasting effects of online social support need to be examined.

  5. Experiences of Family Members of Dying Patients Receiving Palliative Sedation.

    PubMed

    Tursunov, Olga; Cherny, Nathan I; Ganz, Freda DeKeyser

    2016-11-01

    To describe the experience of family members of patients receiving palliative sedation at the initiation of treatment and after the patient has died and to compare these experiences over time.
. Descriptive comparative study.
. Oncology ward at Shaare Zedek Medical Center in Jerusalem, Israel.
. A convenience sample of 34 family members of dying patients receiving palliative sedation. 
. A modified version of a questionnaire describing experiences of family members with palliative sedation was administered during palliative sedation and one to four months after the patient died. Descriptive statistics were used to describe the results of the questionnaire, and appropriate statistical analyses were conducted for comparisons over time.
. Experiences of family members and time.
. Most relatives were satisfied with the sedation and staff support. Palliative sedation was experienced as an ethical way to relieve suffering. However, one-third felt that it shortened the patient's life. An explanation of the treatment was given less than half of the time and was usually given on the same day treatment was started. This explanation was given by physicians and nurses. Many felt that they were not ready for changes in the patient's condition and wanted increased opportunities to discuss the treatment with oncology care providers. No statistically significant differences in experiences were found over time. 
. Relatives' experiences of palliative sedation were generally positive and stable over time. Important experiences included timing of the initiation of sedation, timing and quality of explanations, and communication.
. Nurses should attempt to initiate discussions of the possible role of sedation in the event of refractory symptoms and follow through with continued discussions. The management of refractory symptoms at the end of life, the role of sedation, and communication skills associated with decision making related to palliative sedation should be a

  6. Is long-term virological response related to CCR5 Δ32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

    PubMed Central

    Laurichesse, Jean-Jacques; Taieb, Audrey; Capoulade-Metay, Corinne; Katlama, Christine; Villes, Virginie; Drobacheff-Thiebaud, Marie-Christine; Raffi, François; Chêne, Genevieve; Theodorou, Ioannis; Leport, Catherine

    2010-01-01

    Objective To examine whether CCR5 Δ32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1 infected patients. Methods The genetic sub-study of ANRS CO8 APROCO-COPILOTE cohort included 609 patients who started a protease inhibitor-containing cART in 1997–99. Patients were considered to have a sustained virological response if all plasma HIV-RNA measurements between month 4 and years 3–5 were <500 copies/ml, allowing for a single blip. Virological response was compared between patients heterozygous for CCR5 Δ32 (Δ32/wt) and wild-type patients (wt/wt) from month 4 to year 3 and month 4 to year 5. Logistic regression analysis was used to adjust for baseline demographical data, HIV-RNA, CD4 cell counts, antiretroviral naive status, time spent on antiretroviral therapy at year 3 and 5 and adherence to treatment (month 4 to year 3 and 5). Results Sustained virological response was better in Δ32/wt than in wt/wt patients: 66% versus 52% up to year 3 (p=0.02), nearly significant after adjustment to potential cofounders (p=0.07). Δ32/wt patients had a better virological response, up to year 5, 48% versus 35% (p=0.01), and remained significantly better, after adjustment, associated with a better virological response up to 5 years post initiation of cART (p=0.04). There was no association with CD4 response. Conclusion Δ32/wt deletion is associated with a beneficial virological response to cART on the long-term. Whether this association can be a direct effect of Δ32/wt deletion remains questionable and needs confirmation in other observational studies. PMID:20050936

  7. Health-related quality of life and tolerability in treatment-experienced HIV-1-infected patients on tipranavir versus comparator regimens.

    PubMed

    Huang, I-Chan; Wu, Albert W; Finnern, Henrik W; Thijs, Herbert; Gathe, Joseph C; Fairclough, Diane L

    2008-01-01

    Antiretroviral therapy including tipranavir boosted with ritonavir (TPV/r) has shown superior viral suppression and immunological response compared with comparator ritonavir-boosted protease inhibitor (CPI/r) regimens in treatment-experienced HIV-1-infected patients. This study assesses the influence of adverse events (AEs) on health-related quality of life (HRQOL) and change in HRQOL in patients treated with TPV/r versus CPI/r regimens. Changes in HRQOL over 48 weeks were assessed using Medical Outcomes Study HIV Health Survey (MOS-HIV) data combined from two randomized, open-label, Phase III studies (RESIST-1 and RESIST-2). Generalized estimating equations (GEE) were used to compare physical health and mental health summary scores and 10 subscale scores, and to compare scores of patients with and without AEs. To compare AE incidences in the two treatment groups, AEs were exposure-adjusted. There were 984 patients in the HRQOL analysis. AE occurrence and severity resulted in significantly lower MOS-HIV scores across both treatment arms (P<0.05). Overall incidence of AEs was higher in the CPI/r versus TPV/r group (562.8 versus 514.4 per 100 patient-exposure years); treatment-related AEs were more frequent in the TPV/r group (75.0 versus 56.6 per 100 patient-exposure years). HRQOL was maintained in patients on TPV/r over 48 weeks of treatment across all summary and subscale scores. Compared with CPI/r, TPV/r was associated with a significant but small (SD<0.2) improvement in pain scores (+4.8 points; P<0.05). HRQOL was maintained across both summary and all subscale scores from baseline to 48 weeks in the TPV/r and CPI/r treatment arms, despite the incidence of treatment-related AEs.

  8. Expression and Function of NKG2D Is Impaired in CD8+ T Cells of Chronically HIV-1-Infected Patients Without ART.

    PubMed

    Giuliani, Erica; Vassena, Lia; Desimio, Maria Giovanna; Buonomini, Anna Rita; Malagnino, Vincenzo; Andreoni, Massimo; Doria, Margherita

    2015-12-01

    Increasing line of evidence indicates that the NKG2D-activating receptor plays a relevant role in the effector functions of cytotoxic lymphocytes. In this study, we investigated the expression and function of NKG2D in CD8⁺ T cells from chronically HIV-1-infected patients with or without antiretroviral therapy (ART). We measured by flow cytometry the expression of NKG2D on CD8⁺ T-cell subsets of ART-naive and ART patients as well as seronegative healthy subjects (HIV-neg). An intrapatient analysis before and after ART initiation was also performed. Results were correlated with viral load, CD4⁺ T-cell counts, markers of immune activation (CD38, sCD14), and soluble NKG2D ligands (sMICA and sULBP2). The function of NKG2D on CD8⁺ T cell cytotoxicity was tested by ex vivo degranulation assays. We showed that NKG2D was downregulated on all CD8⁺ T-cell subsets of ART-naive patients. The expression of NKG2D on CD8⁺ T cells inversely correlated with viral load and CD38 expression but not with plasma levels of sMICA and sULBP2. Importantly, we found that NKG2D-mediated costimulation of CD8⁺ T-cell lytic activity was strongly reduced in ART-naive patients if compared with HIV-neg and ART subjects. Finally, intrapatient analysis demonstrated that effective anti-HIV-1 therapy restores NKG2D expression and NKG2D-induced cytotoxicity by CD8⁺ T cells. These data underscore that NKG2D downregulation contributes to impaired CD8⁺ T-cell responses in untreated HIV-1 infection and have implications for monitoring immune functions and response to treatments, and for the development of novel anti-HIV-1 strategies combining ART with drugs that stimulate NKG2D expression and function.

  9. Alisporivir with peginterferon/ribavirin in patients with chronic hepatitis C genotype 1 infection who failed to respond to or relapsed after prior interferon-based therapy: FUNDAMENTAL, a Phase II trial.

    PubMed

    Buti, M; Flisiak, R; Kao, J-H; Chuang, W-L; Streinu-Cercel, A; Tabak, F; Calistru, P; Goeser, T; Rasenack, J; Horban, A; Davis, G L; Alberti, A; Mazzella, G; Pol, S; Orsenigo, R; Brass, C

    2015-07-01

    Alisporivir (ALV) is an oral, investigational host-targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double-blind, placebo-controlled, Phase II study explored the efficacy and safety of ALV with peginterferon-α2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four-hundred-and-fifty-nine patients were randomized (1:1:1:1) to ALV 600 mg once daily (QD), ALV 800 mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48 weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received ≥31 weeks of randomized treatment; patients completed 48 weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P ≤ 0.0131), with highest cEVR rate seen with ALV 400 mg BID (74% vs 36% with PR alone; P < 0.0001). Respective SVR12 rates (key secondary endpoint) were 65% vs 26% in prior relapsers, 63% vs 5% in partial responders and 68% vs 3% in null responders. In patients who received >40 weeks of randomized treatment, the SVR12 rate was 89% for ALV 400 mg BID vs 30% for PR alone (P = 0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400 mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon-free regimens in combination with direct-acting antiviral agents.

  10. Safety and tolerability of ledipasvir/sofosbuvir with and without ribavirin in patients with chronic hepatitis C virus genotype 1 infection: Analysis of phase III ION trials.

    PubMed

    Alqahtani, Saleh A; Afdhal, Nezam; Zeuzem, Stefan; Gordon, Stuart C; Mangia, Alessandra; Kwo, Paul; Fried, Michael; Yang, Jenny C; Ding, Xiao; Pang, Phillip S; McHutchison, John G; Pound, David; Reddy, K Rajender; Marcellin, Patrick; Kowdley, Kris V; Sulkowski, Mark

    2015-07-01

    In phase III studies, treatment with the once-daily fixed-dose combination tablet of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in high rates of sustained virological response (SVR) in patients chronically infected with genotype 1 hepatitis C virus, including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of LDV-SOF with and without RBV. We analyzed treatment-emergent adverse events (AEs) and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080 received LDV/SOF alone) were analyzed. Overall, 308 patients (16%) were African American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index ≥30 kg/m(2) , and 440 (23%) were treatment experienced. Treatment-related AEs occurred in 71% and 45% of patients treated with and without RBV, respectively, including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving RBV with LDV/SOF were more likely to require dose modification, interruptions of treatment resulting from AEs, or require the use of concomitant medications than those receiving LDV/SOF alone. Rates of treatment-related serious AEs and discontinuations resulting from AEs were similarly low (<1%) in both groups. The rate of SVR in those receiving RBV and those not receiving RBV was the same (97%). LDV/SOF plus RBV was associated with a greater incidence of AEs as well as concomitant medication use than LDV/SOF alone. Use of RBV did not impact the efficacy of LDV/SOF regimens in the ION phase III studies. © 2015 by the American Association for the Study of Liver Diseases.

  11. Prognosis of CKD Patients Receiving Outpatient Nephrology Care in Italy

    PubMed Central

    Chiodini, Paolo; Zoccali, Carmine; Borrelli, Silvio; Cianciaruso, Bruno; Di Iorio, Biagio; Santoro, Domenico; Giancaspro, Vincenzo; Abaterusso, Cataldo; Gallo, Ciro; Conte, Giuseppe; Minutolo, Roberto

    2011-01-01

    Summary Background and objectives Prognosis in nondialysis chronic kidney disease (CKD) patients under regular nephrology care is rarely investigated. Design, setting, participants, & measurements We prospectively followed from 2003 to death or June 2010 a cohort of 1248 patients with CKD stages 3 to 5 and previous nephrology care ≥1 year in 25 Italian outpatient nephrology clinics. Cumulative incidence of ESRD or death before ESRD were estimated using the competing-risk approach. Results Estimated rates (per 100 patient-years) of ESRD and death 8.3 (95% confidence interval [CI], 7.4 to 9.2) and 5.9 (95% CI 5.2 to 6.6), respectively. Risk of ESRD and death increased progressively from stages 3 to 5. ESRD was more frequent than death in stage 4 and 5 CKD, whereas the opposite was true in stage 3 CKD. Younger age, lower body mass index, proteinuria, and high phosphate predicted ESRD, whereas older age, diabetes, previous cardiovascular disease, ESRD, proteinuria, high uric acid, and anemia predicted death (P < 0.05 for all). Among modifiable risk factors, proteinuria accounted for the greatest contribution to the model fit for either outcome. Conclusions In patients receiving continuity of care in Italian nephrology clinics, ESRD was a more frequent outcome than death in stage 4 and 5 CKD, but the opposite was true in stage 3. Outcomes were predicted by modifiable risk factors specific to CKD. Proteinuria used in conjunction with estimated GFR refined risk stratification. These findings provide information, specific to CKD patients under regular outpatient nephrology care, for risk stratification that complement recent observations in the general population. PMID:21817127

  12. Clinical review: Traumatic brain injury in patients receiving antiplatelet medication

    PubMed Central

    2012-01-01

    As the population ages, emergency physicians are confronted with a growing number of trauma patients receiving antithrombotic and antiplatelet medication prior to injury. In cases of traumatic brain injury, pre-injury treatment with anticoagulants has been associated with an increased risk of posttraumatic intracranial haemorrhage. Since high age itself is a well-recognised risk factor in traumatic brain injury, this population is at special risk for increased morbidity and mortality. The effects of antiplatelet medication on coagulation pathways in posttraumatic intracranial haemorrhage are not well understood, but available data suggest that the use of these agents increases the risk of an unfavourable outcome, especially in cases of severe traumatic brain injury. Standard laboratory investigations are insufficient to evaluate platelet activity, but new assays for monitoring platelet activity have been developed. Commonly used interventions to restore platelet activity include platelet transfusion and application of haemostatic drugs. Nevertheless, controlled clinical trials have not been carried out and, therefore, clinical practice guidelines are not available. In addition to the risks of the acute trauma, patients are at risk for cardiac events such as life-threatening stent thrombosis if antiplatelet therapy is withdrawn. In this review article, we summarize the pathophysiologic mechanisms of the most commonly used antiplatelet agents and analyse results of studies on the effects of this treatment on patients with traumatic brain injury. Additionally, we focus on opportunities to counteract antiplatelet effects in those patients as well as on considerations regarding the withdrawal of antiplatelet therapy. In those chronically ill patients, an interdisciplinary approach involving intensivists, neurosurgeons as well as cardiologists is often mandatory. PMID:22839302

  13. Prognosis of CKD patients receiving outpatient nephrology care in Italy.

    PubMed

    De Nicola, Luca; Chiodini, Paolo; Zoccali, Carmine; Borrelli, Silvio; Cianciaruso, Bruno; Di Iorio, Biagio; Santoro, Domenico; Giancaspro, Vincenzo; Abaterusso, Cataldo; Gallo, Ciro; Conte, Giuseppe; Minutolo, Roberto

    2011-10-01

    Prognosis in nondialysis chronic kidney disease (CKD) patients under regular nephrology care is rarely investigated. Design, setting, participants, & measurements We prospectively followed from 2003 to death or June 2010 a cohort of 1248 patients with CKD stages 3 to 5 and previous nephrology care ≥1 year in 25 Italian outpatient nephrology clinics. Cumulative incidence of ESRD or death before ESRD were estimated using the competing-risk approach. Estimated rates (per 100 patient-years) of ESRD and death 8.3 (95% confidence interval [CI], 7.4 to 9.2) and 5.9 (95% CI 5.2 to 6.6), respectively. Risk of ESRD and death increased progressively from stages 3 to 5. ESRD was more frequent than death in stage 4 and 5 CKD, whereas the opposite was true in stage 3 CKD. Younger age, lower body mass index, proteinuria, and high phosphate predicted ESRD, whereas older age, diabetes, previous cardiovascular disease, ESRD, proteinuria, high uric acid, and anemia predicted death (P < 0.05 for all). Among modifiable risk factors, proteinuria accounted for the greatest contribution to the model fit for either outcome. In patients receiving continuity of care in Italian nephrology clinics, ESRD was a more frequent outcome than death in stage 4 and 5 CKD, but the opposite was true in stage 3. Outcomes were predicted by modifiable risk factors specific to CKD. Proteinuria used in conjunction with estimated GFR refined risk stratification. These findings provide information, specific to CKD patients under regular outpatient nephrology care, for risk stratification that complement recent observations in the general population.

  14. Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy.

    PubMed

    Lopes, Renato D; Guimarães, Patricia O; Kolls, Bradley J; Wojdyla, Daniel M; Bushnell, Cheryl D; Hanna, Michael; Easton, J Donald; Thomas, Laine; Wallentin, Lars; Al-Khatib, Sana M; Held, Claes; de Barros E Silva, Pedro Gabriel Melo; Alexander, John H; Granger, Christopher B; Diener, Hans-Christoph

    2017-03-29

    We investigated the frequency and characteristics of intracranial hemorrhage (ICH), factors associated with risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients in ARISTOTLE with ICH who received ≥1 dose of study drug (n=18,140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.2%) versus traumatic (28.8%). Apixaban resulted in significantly less ICH (0.33%/year), regardless of type and location, than warfarin (0.80%/year). Independent factors associated with increased risk of ICH were enrollment in Asia or Latin America, older age, prior stroke/transient ischemic attack, and aspirin use at baseline. Among warfarin-treated patients, the median (25th, 75th) time from most recent international normalized ratio (INR) to ICH was 13 (6, 21) days. Median INR prior to ICH was 2.6 (2.1, 3.0); 78.5% of patients had a pre-ICH INR <3.0. After ICH, the modified Rankin scale at discharge was ≥4 in 55.7%, and mortality at 30 days was 43.3%. No difference was observed in the rates of all-cause death post-ICH, regardless of treatment. ICH occurred at a rate of 0.80%/year with warfarin regardless of INR control and 0.33%/year with apixaban, and was associated with high short-term morbidity and mortality. This highlights the clinical relevance of reducing ICH by using apixaban rather than warfarin and avoiding concomitant aspirin, especially in patients with older age.

  15. The lived experience of Lebanese oncology patients receiving palliative care.

    PubMed

    Doumit, Myrna A A; Abu-Saad Huijer, Huda; Kelley, Jane H

    2007-09-01

    The purpose of this study was to uncover the lived experience of Lebanese oncology patients receiving palliative care. The study design was based on the Utrecht School of Phenomenology based on the Dutch school of phenomenology. This study followed purposeful sampling in which ten participants, six women, and four men, with a mean age of 54.4 years were selected. In-depth semi-structured interviews along with observation field notes were used as the source for data collection. Data were analyzed using the hermeneutic phenomenological approach based on the Utrecht School of Phenomenology. The participants highlighted their distress from being dependent; their dislike for pity; their worry for the family and the worry about the family's worry; their reliance on God and divinity; their dislike of the hospital stay; their need to be productive; their fear of pain; and their need to communicate. Specific nursing actions related to the themes would include exploring patients' ideas, beliefs, and experiences regarding pain, and improved communication among patient, family, and the health care providers.

  16. Standardizing of Pathology in Patients Receiving Neoadjuvant Chemotherapy.

    PubMed

    Bossuyt, Veerle; Symmans, W Fraser

    2016-10-01

    The use of neoadjuvant systemic therapy for the treatment of breast cancer patients is increasing. Pathologic response in the form of pathologic complete response (pCR) and grading systems of partial response, such as the residual cancer burden (RCB) system, gives valuable prognostic information for patients and is used as a primary endpoint in clinical trials. The breast cancer and pathology communities are responding with efforts to standardize pathology in patients receiving neoadjuvant chemotherapy. In this review, we summarize the challenges that postneoadjuvant systemic therapy surgical specimens pose and how pathologists and the multidisciplinary team can work together to optimize handling of these specimens. Multidisciplinary communication is essential. A single, standardized approach to macroscopic and microscopic pathologic examination makes it possible to provide reliable response information. This approach employs a map of tissue sections to correlate clinical, gross, microscopic, and imaging findings in order to report the presence of pCR (ypT0 ypN0 and ypT0/is ypN0) versus residual disease, the ypT and ypN stage using the current AJCC/UICC staging system, and the RCB.

  17. Immune deficiency could be an early risk factor for altered insulin sensitivity in antiretroviral-naive HIV-1-infected patients: the ANRS COPANA cohort

    PubMed Central

    Boufassa, Faroudy; Goujard, Cécile; Viard, Jean-Paul; Carlier, Robert; Lefebvre, Bénédicte; Yeni, Patrick; Bouchaud, Olivier; Capeau, Jacqueline; Meyer, Laurence; Vigouroux, Corinne

    2012-01-01

    Background The relationships between immunovirological status, inflammatory markers, insulin resistance and fat distribution have not been studied in recently diagnosed (<1 year) antiretroviral-naïve HIV-1-infected patients. Methods We studied 214 antiretroviral-naïve patients at enrolment in the metabolic sub-study of the ANRS COPANA cohort. We measured clinical, immunovirological and inflammatory parameters, glucose/insulin during oral glucose tolerance test (OGTT), adipokines, subcutaneous and visceral fat surfaces (SAT and VAT, assessed by computed tomography) and the body fat distribution based on dual-energy X-ray absorptiometry (DEXA). Results Median age was 36 years; 28% of the patients were female and 35% of sub-Saharan origin; 20% had low CD4 counts (≤200/mm3). Patients with low CD4 counts were older and more frequently of sub-Saharan Africa origin, had lower BMI but not different SAT/VAT ratio and fat distribution than other patients. They also had lower total, LDL- and HDL-cholesterolemia, higher triglyceridemia and post-OGTT glycemia, higher markers of insulin resistance (insulin during OGTT and HOMA-IR) and of inflammation (hsCRP, IL-6, TNFα, sTNFR1 and sTNFR2). After adjustment for age, sex, geographic origin, BMI and waist circumference, increased insulin resistance was not related to any inflammatory marker. In multivariate analysis, low CD4 count was an independent risk factor for altered insulin sensitivity (β-coefficient for HOMA-IR: +0.90; p=0.001; CD4>500/mm3 as the reference), in addition to older age (β: +0.26 for a 10-year increase; p=0.01) and higher BMI (β: +0.07 for a 1-kg/m2 increase; p=0.003). Conclusions In ART-naive patients, severe immune deficiency but not inflammation could be an early risk factor for altered insulin sensitivity. PMID:22267473

  18. The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy.

    PubMed

    Backx, M; Lewszuk, A; White, J R; Cole, J; Sreedharan, A; van Sanden, S; Diels, J; Lawson, A; Neal, K R; Wiselka, M J; Ito, T; Irving, W L

    2014-03-01

    Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection. © 2013 John Wiley & Sons Ltd.

  19. Evaluation of bleeding in patients receiving direct oral anticoagulants

    PubMed Central

    Hellenbart, Erika L; Faulkenberg, Kathleen D; Finks, Shannon W

    2017-01-01

    Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants. PMID:28860793

  20. Cost-effectiveness of optimized background therapy plus maraviroc for previously treated patients with R5 HIV-1 infection from the perspective of the Spanish health care system.

    PubMed

    Moreno, Santiago; González, Juan; Lekander, Ingrid; Martí, Belén; Oyagüez, Itziar; Sánchez-de la Rosa, Rainel; Casado, Miguel Angel

    2010-12-01

    The aim of this work was to evaluate the cost-effectiveness, from the perspective of the Spanish health care system, of optimized background therapy (OBT) plus maraviroc 300 mg BID versus OBT plus placebo in previously treated patients with R5 HIV-1 infection. A lifetime cohort model was developed, based on 24- and 48-week pooled results from the Maraviroc Versus Optimized Therapy in Viremic Antiretroviral Treatment-Experienced Patients (MOTIVATE) studies 1 and 2, to reflect the Spanish health care system's perspective. Treatment duration was based on clinical trial follow-up from MOTIVATE 1 and 2. Clinical data, cohort characteristics, success probability, CD4 increase rate, CD4 cell status link to disease states, and adverse-event probability were taken from the MOTIVATE trials and other published literature. Other input parameters were taken from published sources. Antiretroviral (ARV) costs were derived from local sources. Non-ARV drug costs were obtained from published literature and a cost database. All costs were calculated as year-2009 euros. The annual discount rate was set at 3.0%. The main outcomes were cost per life-year gained (LYG) and cost per quality-adjusted life-year (QALY) gained. Uncertainty was assessed with one-way and probabilistic sensitivity analyses. In the model analysis, adding maraviroc to OBT was associated with an increase of 0.952 LYG and 0.909 QALY. Total costs were €275,970 for maraviroc plus OBT and €254,655 for placebo plus OBT (difference: €21,315). The incremental cost per LYG was €22,398 and the incremental cost per QALY gained was €23,457. The model appeared to be robust for variations in key parameters. Results from the probabilistic sensitivity analyses indicated that the probability of the cost per QALY being below €30,000 was 99%. Despite the limitations of the model, our analysis suggested that OBT plus maraviroc 300 mg BID is a clinically valuable option, and cost-effective from the perspective of the

  1. Modeling CD4+ cell count increase over a six-year period in HIV-1-infected patients on highly active antiretroviral therapy in Senegal.

    PubMed

    De Beaudrap, Pierre; Etard, Jean-François; Diouf, Assane; Ndiaye, Ibrahima; Guèye, Ndèye Fatou; Guèye, Pape Mandoumbé; Sow, Papa Salif; Mboup, Souleymane; Ndoye, Ibra; Ecochard, René; Eric, Delaporte

    2009-06-01

    To assess the extents and determinants of long-term CD4 cell increases after initiation of antiretroviral therapy (ART), changes in CD4 cell counts were analyzed in a cohort of HIV-1-infected Senegalese using a mixed-effects model. After a median follow-up of 54 months, an average of 483 CD4 cells/mm3 (95% confidence interval [CI] = 331; 680) was reached. The average asymptote level was approximately 421 cells/mm3 (95% CI = 390; 454) in patients with < 200 cells/mm3 at baseline and approximately 500 cells/mm3 in patients with > 200 cells/mm3. The independent predictors of long-term CD4 cell reconstitution were the baseline CD4 cell count and the monthly average viral load over the entire follow-up. This good long-term immune reconstitution, optimal in subjects with low average viral loads and > 200 CD4 cells/mm3 at baseline, argues in favor of the earliest possible access to ART and underlines the importance of strict compliance with the treatment.

  2. A Real Time PCR Platform for the Simultaneous Quantification of Total and Extrachromosomal HIV DNA Forms in Blood of HIV-1 Infected Patients

    PubMed Central

    Canovari, Benedetta; Scotti, Maddalena; Acetoso, Marcello; Valentini, Massimo; Petrelli, Enzo; Magnani, Mauro

    2014-01-01

    Background The quantitative measurement of various HIV-1 DNA forms including total, unintegrated and integrated provirus play an increasingly important role in HIV-1 infection monitoring and treatment-related research. We report the development and validation of a SYBR Green real time PCR (TotUFsys platform) for the simultaneous quantification of total and extrachromosomal HIV-1 DNA forms in patients. This innovative technique makes it possible to obtain both measurements in a single PCR run starting from frozen blood employing the same primers and standard curve. Moreover, due to identical amplification efficiency, it allows indirect estimation of integrated level. To specifically detect 2-LTR a qPCR method was also developed. Methodology/Findings Primers used for total HIV-1 DNA quantification spanning a highly conserved region were selected and found to detect all HIV-1 clades of group M and the unintegrated forms of the same. A total of 195 samples from HIV-1 patients in a wide range of clinical conditions were analyzed with a 100% success rate, even in patients with suppressed plasma viremia, regardless of CD4+ or therapy. No significant correlation was observed between the two current prognostic markers, CD4+ and plasma viremia, while a moderate or high inverse correlation was found between CD4+ and total HIV DNA, with strong values for unintegrated HIV DNA. Conclusions/Significance Taken together, the results support the use of HIV DNA as another tool, in addition to traditional assays, which can be used to estimate the state of viral infection, the risk of disease progression and to monitor the effects of ART. The TotUFsys platform allowed us to obtain a final result, expressed as the total and unintegrated HIV DNA copy number per microgram of DNA or 104 CD4+, for 12 patients within two working days. PMID:25364909

  3. Virological and Immunological Response to Antiretroviral Regimens Containing Maraviroc in HIV Type 1-Infected Patients in Clinical Practice: Role of Different Tropism Testing Results and of Concomitant Treatments

    PubMed Central

    Bianco, Claudia; Bellazzi, Lara Ines; Bruzzone, Bianca; Colao, Grazia; Corsi, Paola; Monno, Laura; Pagano, Gabriella; Paolucci, Stefania; Punzi, Grazia; Setti, Maurizio; Zazzi, Maurizio; De Luca, Andrea

    2014-01-01

    Abstract We assessed the immunovirological response to antiretroviral regimens containing maraviroc in HIV-infected viremic patients with viral tropism predicted by different assays. We selected antiretroviral treatment-experienced HIV-1-infected patients initiating regimens containing maraviroc after different phenotypic or genotypic viral tropism assays, with at least one HIV-1 RNA determination during follow-up. Survival analysis was employed to assess the virological response as time to HIV-1 RNA <50 copies/ml and immunological response as time to a CD4 cell count increase of ≥100/μl from baseline. Predictors of these outcomes were analyzed by multivariate Cox regression models. In 191 treatments with maraviroc, virological response was achieved in 65.4% and the response was modestly influenced by the baseline viral load and concomitant drug activity but not influenced by the type of tropism assay employed. Immunological response was achieved in 58.1%; independent predictors were baseline HIV-1 RNA (per log10 higher: HR 1.29, 95% CI 1.05–1.60) and concomitant therapy with enfuvirtide (HR 2.05, 0.96–4.39) but not tropism assay results. Of 17 patients with baseline R5-tropic virus and available tropism results while viremic during follow-up on maraviroc, seven (41%) showed a tropism switch to non-R5 virus. A significant proportion of experienced patients treated with regimens containing maraviroc achieved virological response. The tropism test type used was not associated with immunovirological response and concomitant treatment with enfuvirtide increased the chance of immunological response. More than half of virological failures with maraviroc were not accompanied by tropism switch. PMID:23971941

  4. Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

    PubMed

    Bouteloup, V; Sabin, C; Mocroft, A; Gras, L; Pantazis, N; Le Moing, V; d'Arminio Monforte, A; Mary-Krause, M; Roca, B; Miro, J M; Battegay, M; Brockmeyer, N; Berenguer, J; Morlat, P; Obel, N; De Wit, S; Fätkenheuer, G; Zangerle, R; Ghosn, J; Pérez-Hoyos, S; Campbell, M; Prins, M; Chêne, G; Meyer, L; Dorrucci, M; Torti, C; Thiébaut, R

    2017-01-01

    The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/μL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/μL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control. © 2016 British HIV Association.

  5. Effectiveness, durability, and safety of darunavir/ritonavir in HIV-1-infected patients in routine clinical practice in Italy: a postauthorization noninterventional study

    PubMed Central

    Antinori, Andrea; Meraviglia, Paola; Monforte, Antonella d’Arminio; Castagna, Antonella; Mussini, Cristina; Bini, Teresa; Gianotti, Nicola; Rusconi, Stefano; Colella, Elisa; Airoldi, Giuseppe; Mancusi, Daniela; Termini, Roberta

    2016-01-01

    Current antiretroviral (ARV) therapy for the treatment of human immunodeficiency virus (HIV-1)-infected patients provides long-term control of viral load (VL). Darunavir (DRV) is a nonpeptidomimetic protease inhibitor approved for use with a ritonavir booster (DRV/r). This study evaluated the effectiveness of DRV/r in combination with other ARV agents in routine clinical practice in Italy. In this descriptive observational study, data on utilization of DRV/r, under the conditions described in the marketing authorization, were collected from June 2009 to December 2012. Effectiveness (VL <50 copies/mL), tolerability, and durability in four patient groups (two DRV/r-experienced, one ARV-experienced DRV/r-naïve, and one ARV-naïve) were analyzed. Secondary objectives included immunological response, safety, and persistence/discontinuation rates. In total, 875 of 883 enrolled patients were included in the analysis: of these, 662 (75.7%) completed the follow-up until the end of 2012 and 213 (24.3%) withdrew from the study earlier. Initial DRV dose was 600 mg twice daily (67.1%) or 800 mg once daily (32.9%). Only 16 patients (1.8%) withdrew from the study due to virological failure. Virological response proportions were higher in patients virologically suppressed at study entry versus patients with baseline VL ≥50 copies/mL in each ARV-experienced group, while there was no consistent difference across study groups and baseline VL strata according to baseline CD4+ cell count. CD4+ cell count increased from study entry to last study visit in all the four groups. DRV/r was well tolerated, with few discontinuations due to study-emergent nonfatal adverse events (3.0% overall, including 2.1% drug-related) or deaths (3.0% overall, all non-drug-related); 35.3% of patients reported ≥1 adverse events. These observational data show that DRV/r was effective and well tolerated in the whole patient population described here. The DRV/r-containing regimen provided viral suppression

  6. Effectiveness, durability, and safety of darunavir/ritonavir in HIV-1-infected patients in routine clinical practice in Italy: a postauthorization noninterventional study.

    PubMed

    Antinori, Andrea; Meraviglia, Paola; Monforte, Antonella d'Arminio; Castagna, Antonella; Mussini, Cristina; Bini, Teresa; Gianotti, Nicola; Rusconi, Stefano; Colella, Elisa; Airoldi, Giuseppe; Mancusi, Daniela; Termini, Roberta

    2016-01-01

    Current antiretroviral (ARV) therapy for the treatment of human immunodeficiency virus (HIV-1)-infected patients provides long-term control of viral load (VL). Darunavir (DRV) is a nonpeptidomimetic protease inhibitor approved for use with a ritonavir booster (DRV/r). This study evaluated the effectiveness of DRV/r in combination with other ARV agents in routine clinical practice in Italy. In this descriptive observational study, data on utilization of DRV/r, under the conditions described in the marketing authorization, were collected from June 2009 to December 2012. Effectiveness (VL <50 copies/mL), tolerability, and durability in four patient groups (two DRV/r-experienced, one ARV-experienced DRV/r-naïve, and one ARV-naïve) were analyzed. Secondary objectives included immunological response, safety, and persistence/discontinuation rates. In total, 875 of 883 enrolled patients were included in the analysis: of these, 662 (75.7%) completed the follow-up until the end of 2012 and 213 (24.3%) withdrew from the study earlier. Initial DRV dose was 600 mg twice daily (67.1%) or 800 mg once daily (32.9%). Only 16 patients (1.8%) withdrew from the study due to virological failure. Virological response proportions were higher in patients virologically suppressed at study entry versus patients with baseline VL ≥50 copies/mL in each ARV-experienced group, while there was no consistent difference across study groups and baseline VL strata according to baseline CD4(+) cell count. CD4(+) cell count increased from study entry to last study visit in all the four groups. DRV/r was well tolerated, with few discontinuations due to study-emergent nonfatal adverse events (3.0% overall, including 2.1% drug-related) or deaths (3.0% overall, all non-drug-related); 35.3% of patients reported ≥1 adverse events. These observational data show that DRV/r was effective and well tolerated in the whole patient population described here. The DRV/r-containing regimen provided viral

  7. Outcomes of Morbidly Obese Patients Receiving Invasive Mechanical Ventilation

    PubMed Central

    Kumar, Gagan; Majumdar, Tilottama; Jacobs, Elizabeth R.; Danesh, Valerie; Dagar, Gaurav; Deshmukh, Abhishek; Taneja, Amit

    2013-01-01

    Background: Critically ill, morbidly obese patients (BMI ≥ 40 kg/m2) are at high risk of respiratory failure requiring invasive mechanical ventilation (IMV). It is not clear if outcomes of critically ill, obese patients are affected by obesity. Due to limited cardiopulmonary reserve, they may have poor outcomes. However, literature to this effect is limited and conflicted. Methods: We used the Nationwide Inpatient Sample from 2004 to 2008 to examine the outcomes of morbidly obese people receiving IMV and compared them to nonobese people. We identified hospitalizations requiring IMV and morbid obesity using International Classification of Diseases, 9th Revision, Clinical Modification codes. Primary outcomes studied were inhospital mortality, rates of prolonged mechanical ventilation (≥ 96 h), and tracheostomy. Multivariable logistic regression was used to adjust for potential confounding variables. We also examined outcomes stratified by number of organs failing. Results: Of all hospitalized, morbidly obese people, 2.9% underwent IMV. Mean age, comorbidity score, and severity of illness were lower in morbidly obese people. The adjusted mortality was not significantly different in morbidly obese people (OR 0.89; 95% CI, 0.74-1.06). When stratified by severity of disease, there was a stepwise increase in risk for mortality among morbidly obese people relative to nonobese people (range: OR, 0.77; 95% CI, 0.58-1.01 for only respiratory failure, to OR, 4.14; 95% CI, 1.11-15.3 for four or more organs failing). Rates of prolonged mechanical ventilation were similar, but rate of tracheostomy (OR 2.19; 95% CI, 1.77-2.69) was significantly higher in patients who were morbidly obese. Conclusions: Morbidly obese people undergoing IMV have a similar risk for death as nonobese people if only respiratory failure is present. When more organs fail, morbidly obese people have increased risk for mortality compared with nonobese people. PMID:23349057

  8. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.

    PubMed

    Afdhal, Nezam; Reddy, K Rajender; Nelson, David R; Lawitz, Eric; Gordon, Stuart C; Schiff, Eugene; Nahass, Ronald; Ghalib, Reem; Gitlin, Norman; Herring, Robert; Lalezari, Jacob; Younes, Ziad H; Pockros, Paul J; Di Bisceglie, Adrian M; Arora, Sanjeev; Subramanian, G Mani; Zhu, Yanni; Dvory-Sobol, Hadas; Yang, Jenny C; Pang, Phillip S; Symonds, William T; McHutchison, John G; Muir, Andrew J; Sulkowski, Mark; Kwo, Paul

    2014-04-17

    Effective treatment for hepatitis C virus (HCV) genotype 1 infection in patients who have not had a sustained virologic response to prior interferon-based therapy represents an unmet medical need. We conducted a phase 3, randomized, open-label study involving patients infected with HCV genotype 1 who had not had a sustained virologic response after treatment with peginterferon and ribavirin, with or without a protease inhibitor. Patients were randomly assigned to receive the NS5A inhibitor ledipasvir and the nucleotide polymerase inhibitor sofosbuvir in a once-daily, fixed-dose combination tablet for 12 weeks, ledipasvir-sofosbuvir plus ribavirin for 12 weeks, ledipasvir-sofosbuvir for 24 weeks, or ledipasvir-sofosbuvir plus ribavirin for 24 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy. Among the 440 patients who underwent randomization and were treated, 20% had cirrhosis and 79% had HCV genotype 1a infection. The rates of sustained virologic response were high in all treatment groups: 94% (95% confidence interval [CI], 87 to 97) in the group that received 12 weeks of ledipasvir-sofosbuvir; 96% (95% CI, 91 to 99) in the group that received 12 weeks of ledipasvir-sofosbuvir and ribavirin; 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir; and 99% (95% CI, 95 to 100) in the group that received 24 weeks of ledipasvir-sofosbuvir and ribavirin. No patient discontinued treatment owing to an adverse event. The most common adverse events were fatigue, headache, and nausea. Treatment with a once-daily, single-tablet regimen of ledipasvir and sofosbuvir resulted in high rates of sustained virologic response among patients with HCV genotype 1 infection who had not had a sustained virologic response to prior interferon-based treatment. (Funded by Gilead Sciences; ION-2 ClinicalTrials.gov number, NCT01768286.).

  9. Validity of the Montreal Cognitive Assessment and the HIV Dementia Scale in the assessment of cognitive impairment in HIV-1 infected patients.

    PubMed

    Janssen, M A M; Bosch, M; Koopmans, P P; Kessels, R P C

    2015-08-01

    The gold standard for evaluating cognitive impairments in HIV-infected patients is to administer an extensive neuropsychological assessment. This may, however, be time-consuming and hence not always feasible in the clinic. Therefore, several brief screening tools have been developed. This study determined the validity of the Montreal Cognitive Assessment (MoCA) and the HIV Dementia Scale (HDS) in detecting cognitive impairment using both the Frascati and cognitive impairment, no dementia (CIND) criteria to classify cognitive impairment in HIV-1 infected patients. The MoCA, HDS, and an extensive neuropsychological assessment, covering nine cognitive domains, were administered in a group of 102 HIV-infected patients who were all on cART and virologically suppressed for at least 1 year. Results show that the areas under the curve (AUCs) for both the MoCA and the HDS were statistically significant, using both the Frascati and the CIND criteria as gold standard. However, the AUCs for the MoCA and HDS did not differ significantly, regardless of the used classification criteria (Frascati: z = 0.37, p = 0.35; CIND: z = -0.62, p = 0.27). Sensitivity of both the MoCA and HDS were low for the recommended cutoff scores (Frascati: MoCA (<26) = 0.56, HDS (<11) = 0.26; CIND: MoCA (<26) = 0.55, HDS (<11) = 0.36). Cutoff scores with good sensitivity and adequate specificity could not be determined for both screening instruments. Therefore, the HDS and MoCA are not recommended as sole instruments to diagnose HIV-associated cognitive impairment.

  10. CD4/CD8 ratio and CD8 counts predict CD4 response in HIV-1-infected drug naive and in patients on cART.

    PubMed

    Sauter, Rafael; Huang, Ruizhu; Ledergerber, Bruno; Battegay, Manuel; Bernasconi, Enos; Cavassini, Matthias; Furrer, Hansjakob; Hoffmann, Matthias; Rougemont, Mathieu; Günthard, Huldrych F; Held, Leonhard

    2016-10-01

    Plasma HIV viral load is related to declining CD4 lymphocytes. The extent to which CD8 cells, in addition to RNA viral load, predict the depletion of CD4 cells is not well characterized so far. We examine if CD8 cell count is a prognostic factor for CD4 cell counts during an HIV infection.A longitudinal analysis is conducted using data from the Swiss HIV cohort study collected between January 2000 and October 2014. Linear mixed regression models were applied to observations from HIV-1-infected treatment naive patients (NAIVE) and cART-treated patients to predict the short-term evolution of CD4 cell counts. For each subgroup, it was quantified to which extent CD8 cell counts or CD4/CD8 ratios are prognostic factors for disease progression.In both subgroups, 2500 NAIVE and 8902 cART patients, past CD4 cells are positively (P < 0.0001) and past viral load is negatively (P < 0.0001) associated with the outcome. Including additionally past CD8 cell counts improves the fit significantly (P < 0.0001) and increases the marginal explained variation 31.7% to 40.7% for the NAIVE and from 44.1% to 50.7% for the cART group. The past CD4/CD8 ratio (instead of the past CD8 level) is positively associated with the outcome, increasing the explained variation further to 41.8% for NAIVE and 51.9% for cART.

  11. CD4/CD8 ratio and CD8 counts predict CD4 response in HIV-1-infected drug naive and in patients on cART

    PubMed Central

    Sauter, Rafael; Huang, Ruizhu; Ledergerber, Bruno; Battegay, Manuel; Bernasconi, Enos; Cavassini, Matthias; Furrer, Hansjakob; Hoffmann, Matthias; Rougemont, Mathieu; Günthard, Huldrych F; Held, Leonhard

    2016-01-01

    Abstract Plasma HIV viral load is related to declining CD4 lymphocytes. The extent to which CD8 cells, in addition to RNA viral load, predict the depletion of CD4 cells is not well characterized so far. We examine if CD8 cell count is a prognostic factor for CD4 cell counts during an HIV infection. A longitudinal analysis is conducted using data from the Swiss HIV cohort study collected between January 2000 and October 2014. Linear mixed regression models were applied to observations from HIV-1-infected treatment naive patients (NAIVE) and cART-treated patients to predict the short-term evolution of CD4 cell counts. For each subgroup, it was quantified to which extent CD8 cell counts or CD4/CD8 ratios are prognostic factors for disease progression. In both subgroups, 2500 NAIVE and 8902 cART patients, past CD4 cells are positively (P < 0.0001) and past viral load is negatively (P < 0.0001) associated with the outcome. Including additionally past CD8 cell counts improves the fit significantly (P < 0.0001) and increases the marginal explained variation 31.7% to 40.7% for the NAIVE and from 44.1% to 50.7% for the cART group. The past CD4/CD8 ratio (instead of the past CD8 level) is positively associated with the outcome, increasing the explained variation further to 41.8% for NAIVE and 51.9% for cART. PMID:27759638

  12. A mathematical prognosis model for pancreatic cancer patients receiving immunotherapy.

    PubMed

    Li, Xuefang; Xu, Jian-Xin

    2016-10-07

    Pancreatic cancer is one of the most deadly types of cancer since it typically spreads rapidly and can seldom be detected in its early stage. Pancreatic cancer therapy is thus a challenging task, and appropriate prognosis or assessment for pancreatic cancer therapy is of critical importance. In this work, based on available clinical data in Niu et al. (2013) we develop a mathematical prognosis model that can predict the overall survival of pancreatic cancer patients who receive immunotherapy. The mathematical model incorporates pancreatic cancer cells, pancreatic stellate cells, three major classes of immune effector cells CD8+ T cells, natural killer cells, helper T cells, and two major classes of cytokines interleukin-2 (IL-2) and interferon-γ (IFN-γ). The proposed model describes the dynamic interaction between tumor and immune cells. In order for the model to be able to generate appropriate prognostic results for disease progression, the distribution and stability properties of equilibria in the mathematical model are computed and analysed in absence of treatments. In addition, numerical simulations for disease progression with or without treatments are performed. It turns out that the median overall survival associated with CIK immunotherapy is prolonged from 7 to 13months compared with the survival without treatment, this is consistent with the clinical data observed in Niu et al. (2013). The validity of the proposed mathematical prognosis model is thus verified. Our study confirms that immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model.

  13. Hepatic cyst penetration of cefazolin in patients receiving aspiration sclerotherapy.

    PubMed

    Lantinga, M A; Wijnands, T F M; Te Morsche, R H M; de Sévaux, R G L; Kuipers, S; Allegaert, K; Burger, D; Drenth, J P H

    2016-09-01

    Hepatic cyst infection is a potentially severe complication in cystic disease. Treatment demands effective antibiotic concentrations within the infected cyst. The aim of this study was to use elective hepatic cyst drainage as a unique pharmacokinetic model to investigate whether cefazolin, a first-generation cephalosporin, is able to penetrate hepatic cysts. Patients scheduled to undergo percutaneous aspiration sclerotherapy of a symptomatic non-infected, non-neoplastic hepatic cyst were eligible for this study. All participants received a single perioperative prophylactic dose of cefazolin (1000 mg, intravenously). We collected blood and cyst fluid samples to determine total and unbound cefazolin concentrations using HPLC. The primary outcome was hepatic cyst penetration, expressed as the ratio (%) of unbound concentration of cefazolin in cyst fluid to plasma (both in mg/L). We included eight patients [male = 25%, median age = 60 years (IQR 54-75), median estimated glomerular filtration rate = 97 mL/min/1.73 m(2) (IQR 67-102) and median serum albumin = 40 g/L (IQR 37-40)]. We detected low concentrations of unbound cefazolin in cyst fluid (≤1.0 mg/L). The median plasma unbound cefazolin peak level (immediately after cefazolin administration) was 36.6 mg/L (IQR 23.7-54.1) and the level at the time of cyst fluid aspiration was 16.1 mg/L (IQR 13.0-20.1). In total, the hepatic cyst penetration of free cefazolin was only 2.2% (IQR 0.7-5.2). We developed a study model to investigate the penetration of antibiotics into hepatic cysts. Cefazolin did not reach adequate intracystic concentrations. Future studies should explore alternatives. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Properties of a new mouthrinse for patients receiving radiation therapy.

    PubMed

    Patel, M; Ndlovu, N N; Owen, C P; Veale, R

    2010-10-01

    Patients receiving radiation therapy due to oral cancer develop complications such as hyposalivation, mucositis, oral infections, dental hypersensitivity and caries. Mouthrinses can alleviate some of these problems. To investigate the in vitro antimicrobial properties and cytotoxicity of an experimental mouthrinse. The mouthrinse contained 30% hexylene glycol (glycerine), 7% potassium nitrate and 0.025% sodium fluoride. The minimal inhibitory concentration (MIC) of these ingredients and the mixture was determined for C. albicans, S. aureus and S. mutans over 24 hours at different concentrations. The MICs of two commercial mouthrinses, Corsodyl and Plax, were also determined using the same organisms. All mouthrinses were then tested to determine the percentage kill over 1, 2, and 3 minutes. The MICs for hexylene glycol were 10%, 30% and 10% for C. albicans, S. aureus and S. mutons respectively. Potassium nitrate and sodium fluoride had no antimicrobial effects. The MIC of Corsodyl was 0.016 mg/ml for all the test organisms. The MIC for Plax varied from 0.0002 mg/ml to 0.001 mg/ml. The kill rates for all mouthrinses were acceptable, with no statistical differences between them. The experimental mouthrinse was not toxic to human oesophageal SCC cells after 1 minute exposure. At the time of the experiment, the costs of a similar quantity of the experimental mouthrinse, Corsodyl and Plax were R5.24, R30.00 and R10.00 respectively. The experimental mouthrinse was cost-effective and proved to have an antimicrobial effect and could be used safely to alleviate oral infections, desensitize teeth, improve oral hygiene and control dental caries in cancer patients after radiation therapy.

  15. Mortality, AIDS-morbidity and loss to follow-up by current CD4 cell count among HIV-1 infected adults receiving antiretroviral therapy in Africa and Asia: data from the ANRS 12222 collaboration

    PubMed Central

    Gabillard, Delphine; Lewden, Charlotte; Ndoye, Ibra; Moh, Raoul; Ségéral, Olivier; Tonwe-Gold, Besigin; Etard, Jean-François; Pagnaroat, Men; Fournier-Nicolle, Isabelle; Eholié, Serge; Konate, Issouf; Minga, Albert; Mpoudi-Ngolé, Eitel; Koulla-Shiro, Sinata; Zannou, Djimon Marcel; Anglaret, Xavier; Laurent, Christian

    2013-01-01

    Background In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses and inform decisions. Methods We pooled data from 13 research cohorts in five sub-Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire and Senegal) and two Asian (Cambodia and Laos) countries. HIV-infected adults (≥18 years) who received ART in 1998-2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results Overall 3,917 adults (62% women) on ART were followed-up during 10,154 person-years. In the ≤50, 51-100, 101-200, 201-350, 351-500, 501-650 and >650/mm3 CD4 cells strata, death rates were: 20.6, 11.8, 6.7, 3.3, 1.8, 0.9 and 0.3 per 100 person-years; AIDS rates were: 50.5, 32.9, 11.5, 4.8, 2.8, 2.2 and 2.2 per 100 person-years; and loss to follow-up rates were: 4.9, 6.1, 3.5, 3.1, 2.9, 1.7 and 1.2 per 100 person-years, respectively. Mortality and morbidity were higher during the first year following ART initiation. Conclusion In these resource-limited settings, death and AIDS rates remained substantial after ART initiation, even in individuals with high CD4 cell counts. Ensuring earlier ART initiation and optimizing case finding and treatment for AIDS-defining diseases should be seen as priorities. PMID:23274931

  16. Immune deficiency could be an early risk factor for altered insulin sensitivity in antiretroviral-naive HIV-1-infected patients: the ANRS COPANA cohort.

    PubMed

    Boufassa, Faroudy; Goujard, Cécile; Viard, Jean-Paul; Carlier, Robert; Lefebvre, Bénédicte; Yeni, Patrick; Bouchaud, Olivier; Capeau, Jacqueline; Meyer, Laurence; Vigouroux, Corinne

    2012-01-01

    The relationships between immunovirological status, inflammatory markers, insulin resistance and fat distribution have not been studied in recently diagnosed (<1 year) antiretroviral-naive HIV-1-infected patients. We studied 214 antiretroviral-naive patients at enrolment in the metabolic substudy of the ANRS COPANA cohort. We measured clinical, immunovirological and inflammatory parameters, glucose/insulin during oral glucose tolerance test (OGTT), adipokines, subcutaneous and visceral fat surfaces (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT], assessed by computed tomography) and the body fat distribution based on dual-energy X-ray absorptiometry (DEXA). Median age was 36 years; 28% of the patients were female and 35% of sub-Saharan origin; 20% had low CD4(+) T-cell counts (≤200/mm(3)). Patients with low CD4(+) T-cell counts were older and more frequently of sub-Saharan Africa origin, had lower body mass index (BMI) but no different SAT/VAT ratio and fat distribution than other patients. They also had lower total, low-density lipoprotein and high-density lipoprotein cholesterolaemia, higher triglyceridaemia and post-OGTT glycaemia, higher markers of insulin resistance (insulin during OGTT and homeostasis model assessment of insulin resistance) and of inflammation (high-sensitivity C-reactive protein, IL-6, tumour necrosis factor (TNF)-α, sTNFR1 and sTNFR2). After adjustment for age, sex, geographic origin, BMI and waist circumference, increased insulin resistance was not related to any inflammatory marker. In multivariate analysis, low CD4(+) T-cell count was an independent risk factor for altered insulin sensitivity (β-coefficient for HOMA-IR: +0.90; P=0.001; CD4(+) T-cell count >500/mm(3) as the reference), in addition to older age (β: +0.26 for a 10-year increase; P=0.01) and higher BMI (β: +0.07 for a 1-kg/m(2) increase; P=0.003). In ART-naive patients, severe immune deficiency but not inflammation could be an early risk factor for

  17. Changes in the levels of some acute-phase proteins in human immunodeficiency virus-1 infected patients, following interleukin-2 treatment

    PubMed Central

    Barbai, V H; Ujhelyi, E; Szlávik, J; Vietorisz, I; Varga, L; Fey, E; Füst, G; Bánhegyi, D

    2010-01-01

    Intermittent interleukin (IL)-2 administration to human immunodeficiency virus (HIV)-1 infected patients is well documented and generally used, but there is limited information about the changes of acute-phase protein (APP) levels in response to this treatment. Fifteen patients undergoing highly active anti-retroviral therapy (HAART) treatment, with undetectable viral load, but low CD4+ cell count (<300/µl), have been treated with 3·6 M IU Proleukine® administered twice daily by subcutaneous injection over 5 days. C-reactive protein (CRP), d-dimer, C3, C9, C1-inh and alpha-2HS glycoprotein levels were measured immediately before IL-2 administration, as well as on day 5 and 2–3 weeks thereafter. After IL-2 administration, both mean d-dimer and CRP levels increased significantly (P < 0·001), but returned (P < 0·001) to baseline within the subsequent 2–3 weeks. Alpha-2HS glycoprotein decreased immediately after IL-2 administration. No significant differences were detected in the levels of C3, C9 and C1-inh. A significant, positive correlation (r = 0·5178, P = 0·0008) was ascertained between the changes of CRP level, measured immediately before as well as 5 days after IL-2 administration, and changes in CD4 T cell counts measured 2–3 weeks before and after treatment, respectively. IL-2 administration induces rapid elevation of two major APPs (CRP, d-dimer). The positive correlation observed between the changes of CRP levels and CD4+ cell counts after IL-2 administration may indicate that the abrupt, but transitory overproduction of CRP might contribute to the CD4+ cell count-increasing effect of the drug and/ or may be associated with serious side effects. PMID:20408859

  18. Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients.

    PubMed

    Depincé-Berger, Anne-Emmanuelle; Vergnon-Miszczycha, Delphine; Girard, Alexandre; Frésard, Anne; Botelho-Nevers, Elisabeth; Lambert, Claude; Del Tedesco, Emilie; Genin, Christian; Pozzetto, Bruno; Lucht, Frédéric; Roblin, Xavier; Bourlet, Thomas; Paul, Stéphane

    2016-06-30

    A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in the gut. In this study, we analyzed the characteristics of HIV rectal reservoir of long-term treated patients, regarding their blood CD4(+) T cells count at the time of cART initiation. Twenty-four consenting men were enrolled: 9 exhibiting a CD4(+) T cells count >350/mm(3) ("high-level CD4 group") and 15 < 350/mm(3) ("low-level CD4 group") in blood, at the start of cART. An immunophenotypical analysis of T and B cells subpopulations was performed in blood and rectal biopsies. HIV cell-associated DNA loads and qualitative intra-cellular RNA were determined in both compartments. The ratio of CD4(+)/CD8(+) T cells was significantly decreased in the blood but not in the rectum of the "low-level CD4 group" of patients. The alteration in β7(+) CD4(+) T cells homing was higher in this group and was correlated to a low ratio of CD4(+)/CD8(+) T cells in blood. An initiation of cART in men exhibiting a low-level CD4 count was also associated with an alteration of B cells maturation. HIV blood and gut DNA reservoirs were significantly lower in the "high-level CD4 group" of men. A high HIV DNA level was associated to a detectable intracellular HIV RNA in rectum. An early initiation of cART could significantly preserve gut immunity and limit the viral reservoir constitution.

  19. [Dermatomiositis and evans syndrome associated with HTLV-1 infection].

    PubMed

    Loja-Oropeza, David; Zavala-Flores, Ernesto; Vilca-Vasquez, Maricela

    2016-03-01

    A 55-year-old female patient, born in Ayacucho, with a history of dermatomyositis for 3 years, who received irregular treatment with prednisone. Two months prior to admission, she presented with autoinmune hemolytic anemia and idiopathic thrombocytopenic purpura. The patient received methylprednisolone pulse therapy and packed red blood cells transfusions. Upon admission, she was drowsy, with a poor overall status, marked weight loss, dehydration, with presence of livedo reticularis in her lower extremities, and onychodystrophy and onycholysis on the toes of both feet. Western blot test was positive for human T-lymphotropic virus type 1 (HTLV-1). The patient evolved with recurrent hypoglycemia. Therefore, we report a case of dermatomyositis and Evans syndrome in the context of an HTLV-1 infection.

  20. Large osteoclasts in pediatric osteogenesis imperfecta patients receiving intravenous pamidronate.

    PubMed

    Cheung, Moira S; Glorieux, Francis H; Rauch, Frank

    2009-04-01

    Intravenous pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). Changes in the appearance of osteoclasts have previously been noted in children receiving pamidronate and have been interpreted as signs of toxicity. In this study, we analyzed osteoclast parameters in paired iliac bone specimens before and after 2-4 yr of cyclical intravenous pamidronate therapy in 44 pediatric OI patients (age range: 1.4-17.5 yr; 21 girls). During pamidronate treatment, average osteoclast diameter and the mean number of nuclei present per osteoclast increased by 18% (p = 0.02) and 43% (p < 0.001), respectively. The number of samples containing large osteoclasts (LOcs, diameter > 50 mum) increased from 6 (14%) before treatment to 23 (52%) after pamidronate therapy (p < 0.001 by chi(2) test). Post-treatment samples containing LOcs had a greater core width (p = 0.04) and a higher cancellous bone volume per tissue volume (p < 0.001), because cancellous bone volume had increased more during pamidronate treatment (p < 0.001). Osteoclast number and surface were higher in samples with LOcs, but there was no difference in cancellous bone formation parameters. The presence of LOcs was independent of OI type, type of collagen type I mutation, lumbar spine BMD, and other clinical or biochemical measures. In conclusion, this study did not show any indication that LOcs during pamidronate treatment are indicative of toxicity. It seems more likely that the observed abnormalities in osteoclast morphology are part of the mechanism of action of this drug.

  1. Long-term efficacy, safety, and tolerability of rilpivirine (RPV, TMC278) in HIV type 1-infected antiretroviral-naive patients: week 192 results from a phase IIb randomized trial.

    PubMed

    Wilkin, Aimee; Pozniak, Anton L; Morales-Ramirez, Javier; Lupo, Sergio H; Santoscoy, Mario; Grinsztejn, Beatriz; Ruxrungtham, Kiat; Rimsky, Laurence T; Vanveggel, Simon; Boven, Katia

    2012-05-01

    TMC278-C204 (NCT00110305), a 96-week trial of the nonnucleoside reverse transcription inhibitor (NNRTI) rilpivirine (RPV, TMC278) in 368 HIV-1-infected, treatment-naive patients, was extended to investigate long-term safety and efficacy. Week 192 analysis results are presented. This was a long-term follow-up of a Phase IIb, randomized trial. No significant RPV dose-response relationships with respect to the primary endpoint (composite ITT-TLOVR algorithm) were observed at week 48 or 96. All RPV-treated patients were switched to open-label 75 mg qd at week 96 and then to 25 mg qd, the Phase III dose, at approximately week 144 as it gave the best benefit-risk balance. All control patients continued receiving open-label efavirenz (EFV) 600 mg qd. At week 192, 59% of RPV- and 61% of EFV-treated patients maintained confirmed viral load <50 copies/ml (ITT-TLOVR algorithm). The mean changes from baseline in CD4 cell count were similar in both groups (RPV: 210 cells/mm(3) vs. EFV: 225 cells/mm(3)). No new safety concerns were noted between week 48 and 192. In the week 192 analysis, RPV compared with EFV was associated with a lower overall incidence of grade 2-4 adverse events (AEs) at least possibly related to treatment, including rash (p<0.001) and neurologic AEs (p<0.05 Fisher's exact test, post hoc analyses) Incidences of serious AEs, grade 3 or 4 AEs, and discontinuations due to AEs were similar across groups. Increases in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were significantly lower with RPV than with EFV. RPV continued to show sustained efficacy similar to EFV at week 192 with a generally more favorable safety profile.

  2. Viral Genetic Diversity and Polymorphisms in a Cohort of HIV-1-Infected Patients Eligible for Initiation of Antiretroviral Therapy in Abuja, Nigeria.

    PubMed

    Diallo, Karidia; Zheng, Du-Ping; Rottinghaus, Erin K; Bassey, Orji; Yang, Chunfu

    2015-05-01

    Studying the genetic diversity and natural polymorphisms of HIV-1 would benefit our understanding of HIV drug resistance (HIVDR) development and predict treatment outcomes. In this study, we have characterized the HIV-1 genetic diversity and natural polymorphisms at the 5' region of the pol gene encompassing the protease (PR) and reverse transcriptase (RT) from 271 plasma specimens collected in 2008 from HIV-1-infected patients who were eligible for initiating antiretroviral therapy in Abuja (Nigeria). The analysis indicated that the predominant subtype was subtype G (31.0%), followed by CRF02-AG (19.2 %), CRF43-02G (18.5%), and A/CRF36-cpx (11.4%); the remaining (19.9%) were other subtypes and circulating (CRF) and unique (URF) recombinant forms. Recombinant viruses (68.6%) were the major viral strains in the region. Eighty-four subtype G sequences were further mainly classified into two major and two minor clusters; sequences in the two major clusters were closely related to the HIV-1 strains in two of the three major subtype G clusters detected worldwide. Those in the two minor clusters appear to be new subtype G strains circulating only in Abuja. The pretreatment DR prevalence was <3%; however, numerous natural polymorphisms were present. Eleven polymorphic mutations (G16E, K20I, L23P, E35D, M36I, N37D/S/T, R57K, L63P, and V82I) were detected in the PR that were subtype or CRF specific while only three mutations (D123N, I135T, and I135V) were identified in the RT. Overall, this study indicates an evolving HIV-1 epidemic in Abuja with recombinant viruses becoming the dominant strains and the emergence of new subtype G strains; pretreatment HIVDR was low and the occurrence of natural polymorphism in the PR region was subtype or CRF dependent.

  3. Cost effectiveness of direct-acting antiviral therapy for treatment-naive patients with chronic HCV genotype 1 infection in the veterans health administration.

    PubMed

    Chan, Kee; Lai, Mai Ngan; Groessl, Erik J; Hanchate, Amresh D; Wong, John B; Clark, Jack A; Asch, Steven M; Gifford, Allen L; Ho, Samuel B

    2013-11-01

    The Veterans Health Administration (VHA) is the largest single provider of care for hepatitis C virus (HCV) infection in the United States. We analyzed the cost effectiveness of treatment with the HCV protease inhibitors boceprevir and telaprevir in a defined managed care population of 102,851 patients with untreated chronic genotype 1 infection. We used a decision-analytic Markov model to examine 4 strategies: standard dual-therapy with pegylated interferon-alfa and ribavirin (PR), the combination of boceprevir and PR triple therapy, the combination of telaprevir and PR, or no antiviral treatment. A sensitivity analysis was performed. Sources of data included published rates of disease progression, the census bureau, and VHA pharmacy and hospitalization cost databases. The estimated costs for treating each patient were $8000 for PR, $31,300 for boceprevir and PR, and $41,700 for telaprevir and PR. Assuming VHA treatment rates of 22% and optimal rates of sustained virologic response, PR, boceprevir and PR, and telaprevir and PR would reduce relative liver-related deaths by 5.2%, 10.9%, and 11.5%, respectively. Increasing treatment rates to 50% would reduce liver-related deaths by 12%, 24.7%, and 26.1%, respectively. The incremental cost-effectiveness ratios were $29,184/quality-adjusted life-years for boceprevir and PR and $44,247/quality-adjusted life-years for telaprevir and PR vs only PR. With the current 22% treatment rate, total system-wide costs to adopt boceprevir and PR or telaprevir and PR would range from $708 to $943 million. Despite substantial up-front costs of treating HCV-infected patients in the VHA with PR, or telaprevir and PR, each regimen improves quality of life and extends life expectancy by reducing liver-related morbidity and mortality, and should be cost effective. Further efforts to expand access to direct-acting antiviral therapy are warranted. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. A Clinical Study on Administration of Opioid Antagonists in Terminal Cancer Patients: 7 Patients Receiving Opioid Antagonists Following Opioids among 2443 Terminal Cancer Patients Receiving Opioids.

    PubMed

    Uekuzu, Yoshihiro; Higashiguchi, Takashi; Futamura, Akihiko; Ito, Akihiro; Mori, Naoharu; Murai, Miyo; Ohara, Hiroshi; Awa, Hiroko; Chihara, Takeshi

    2017-03-01

    There have been few detailed reports on respiratory depression due to overdoses of opioids in terminal cancer patients. We investigated the situation of treatment with opioid antagonists for respiratory depression that occurred after administration of opioid at optimal doses in terminal cancer patients, to clarify pathological changes as well as causative factors. In 2443 terminal cancer patients receiving opioids, 7 patients (0.3%) received opioid antagonists: 6, morphine (hydrochloride, 5; sulfate, 1); 1, oxycodone. The median dosage of opioids was 13.3 mg/d, as converted to morphine injection. Respiratory depression occurred on this daily dose in 4 patients and after changed dose and route in 3 patients. Opioids were given through the vein in 6 patients and by the enteral route in 1 patient. Concomitant drugs included nonsteroidal anti-inflammatory drugs in 3 patients and zoledronic acid in 2 patients. In morphine-receiving patients, renal functions were significantly worsened at the time of administration of an opioid antagonist than the day before the start of opioid administration. These findings indicate that the proper use of opioids was safe and acceptable in almost all terminal cancer patients. In rare cases, however, a risk toward respiratory depression onset is indicated because morphine and morphine-6-glucuronide become relatively excessive owing to systemic debility due to disease progression, especially respiratory and renal dysfunctions. At the onset of respiratory depression, appropriate administration of an opioid antagonist mitigated the symptoms. Thereafter, opioid switching or continuous administration at reduced dosages of the same opioids prevented the occurrence of serious adverse events.

  5. No relationship between TNF-α genetic variants and combination antiretroviral therapy-related lipodystrophy syndrome in HIV type 1-infected patients: a case-control study and a meta-analysis.

    PubMed

    Veloso, Sergi; Olona, Montserrat; Peraire, Joaquim; Viladés, Consuelo; Pardo, Pedro; Domingo, Pere; Asensi, Victor; Broch, Montserrat; Aguilar, Carmen; López-Dupla, Miguel; Aragonés, Gerard; Garcia-Pardo, Graciano; Sirvent, Joan-Josep; Vendrell, Joan; Richart, Cristóbal; Vidal, Francesc

    2011-02-01

    Tumor necrosis factor alpha (TNF-α) is thought to be involved in the pathogenic and metabolic events associated with HIV-1 infection. We assessed whether carriage of the TNF-α gene promoter single nucleotide polymorphism (SNP) is associated with lipodystrophy and metabolic derangements in HIV-1-infected patients treated with cART. We also assessed variations in TNF-α receptor plasma levels. The study group comprised 286 HIV-1-infected patients (133 with and 153 without lipodystrophy) and 203 uninfected controls (UC). TNF-α -238G > A, -308G > A, and -863 C > A SNP were assessed using PCR-RFLPs on white cell DNA. Plasma sTNF-α R1 and R2 levels were measured by ELISA. Student's t test, the χ(2) test, Pearson correlations, and the logistic regression test were performed for statistical analysis. The TNF-α -308G > A SNP was significantly associated with lipodystrophy in the univariate analysis (p = 0.04). This association, however, was no longer significant in the multivariate analysis. A meta-analysis of the published literature and our own data, which included 284 patients with lipodystrophy and 338 without lipodystrophy, showed that there was no relationship between the TNF-α -238G > A and -308G > A SNP and lipodystrophy (p > 0.05 for all comparisons). HIV-1-infected patients had greater sTNF-α R2 plasma levels than UC (p = 0.001) whereas sTNF-α R1 and R2 levels were not significantly different in both the HIV-1-infected cohorts, lipodystrophy vs. nonlipodystrophy (p = NS). In our cohort of white Spaniards the TNF-α -238G > A, -308G > A, and -863C > A SNP were not associated with lipodystrophy in HIV-1-infected patients treated with cART. This finding was replicated in a meta-analysis of the published data, which showed no associations between the TNF-α -238G > A and -308G > A SNP and lipodystrophy. In HIV-1-infected patients under cART there is a systemic overproduction of sTNF-α R2, which is unrelated to

  6. Alcohol in Primary Care. Differential characteristics between alcohol-dependent patients who are receiving or not receiving treatment.

    PubMed

    Barrio, Pablo; Miquel, Laia; Moreno-España, Jose; Martínez, Alicia; Ortega, Lluisa; Teixidor, Lidia; Manthey, Jakob; Rehm, Jürgen; Gual, Antoni

    2016-03-02

    primary health care services for other reasons. The aim of the present study is to describe the differential characteristics of AD patients in primary care, distinguishing between those who receive treatment and those who do not, and their reasons for not seeking it. In a cross-sectional study patients were evaluated by their general practitioner (GP) and interviewed by a member of the research team. Sociodemographic, diagnostic and clinical data were collected. From 1,372 patients interviewed in Catalonia, 118 (8.6%) were diagnosed as AD. These patients showed a lower socioeconomic status (48.3% vs 33.3%, odds ratio 2.02), higher unemployment rates (32.2% vs 19.2 %, odds ratio 2.11), and greater psychological distress and disability. Patients with AD receiving treatment (16.9%), were older (44 vs 36 years of age), reported higher unemployment rates (66% vs 25.5%, odds ratio 6.32) and higher daily alcohol consumption (61.5 vs 23.7 grams), suggesting a more advanced disease. Patients with AD in general showed a higher degree of comorbidity compared to other patients, with patients in treatment showing the most elevated level. The main reasons given for not seeking treatment were shame, fear of giving up drinking and barriers to treatment. Taken together, the data suggest the need to implement earlier strategies for the detection and treatment of AD.

  7. Comparing Relaxation Programs for Breast Cancer Patients Receiving Radiotherapy

    Cancer.gov

    In this study, women with breast cancer who have had surgery and are scheduled to undergo radiation therapy will be randomly assigned to one of two different stretching and relaxation programs or to a control group that will receive usual care.

  8. Mixed systemic amyloidosis in a patient receiving long term haemodialysis.

    PubMed Central

    Fernandez-Alonso, J; Rios-Camacho, C; Valenzuela-Castaño, A; Hernanz-Mediano, W

    1994-01-01

    A 64 year old woman had been receiving haemodialysis for 11 years. She had a history of chronic renal failure, caused by probable chronic pyelonephritis, and dialysis arthropathy. She died of acute pulmonary oedema and haemorrhage. At necropsy, histological, immunohistochemical, and ultrastructural studies showed widespread visceral deposits of beta 2-microglobulin (beta 2-M) and AA amyloid. Images PMID:8063944

  9. Trends in Transmission of Drug Resistance and Prevalence of Non-B Subtypes in Patients with Acute or Recent HIV-1 Infection in Barcelona in the Last 16 Years (1997-2012)

    PubMed Central

    Nicolas, David; Parera, Marta; López-Diéguez, María; Romero, Anabel; Agüero, Fernando; Marcos, María Ángeles; Manzardo, Christian; Zamora, Laura; Gómez-Carrillo, Manuel; Gatell, José María; Pumarola, Tomás; Miró, José María

    2015-01-01

    Objectives To evaluate the prevalence of transmitted drug resistance (TDR) and non-B subtypes in patients with acute/recent HIV-1 infection in Barcelona during the period 1997-2012. Methods Patients from the “Hospital Clínic Primary HIV-1 Infection Cohort” with a genotyping test performed within 180 days of infection were included. The 2009 WHO List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistance was used for estimating the prevalence of TDR and phylogenetic analysis for subtype determination. Results 189 patients with acute/recent HIV-1 infection were analyzed in 4 time periods (1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64). The proportion of patients with acute/recent HIV-1 infection with respect to the total of newly HIV-diagnosed patients in our center increased over the time and was 2.18%, 3.82%, 4.15% and 4.55% for the 4 periods, respectively (p=0.005). The global prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study period (p=0.2). The increase in the last period was driven by protease-inhibitor and nucleoside-reverse-transcriptase-inhibitor resistance mutations while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR of more than one family decreased. The overall prevalence of non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study period (p=0.01). B/F recombinants, B/G recombinants and subtype F emerged in the last period. We also noticed an increase in the number of immigrant patients (p=0.052). The proportion of men-who-have-sex-with-men (MSM) among patients with acute/recent HIV-1 infection increased over the time (p=0.04). Conclusions The overall prevalence of TDR in patients with acute/recent HIV-1 infection in Barcelona was 9%, and it has stayed relatively stable in recent years. Non-B subtypes and immigrants proportions progressively increased. PMID:26039689

  10. Trends in Transmission of Drug Resistance and Prevalence of Non-B Subtypes in Patients with Acute or Recent HIV-1 Infection in Barcelona in the Last 16 Years (1997-2012).

    PubMed

    Ambrosioni, Juan; Sued, Omar; Nicolas, David; Parera, Marta; López-Diéguez, María; Romero, Anabel; Agüero, Fernando; Marcos, María Ángeles; Manzardo, Christian; Zamora, Laura; Gómez-Carrillo, Manuel; Gatell, José María; Pumarola, Tomás; Miró, José María

    2015-01-01

    To evaluate the prevalence of transmitted drug resistance (TDR) and non-B subtypes in patients with acute/recent HIV-1 infection in Barcelona during the period 1997-2012. Patients from the "Hospital Clínic Primary HIV-1 Infection Cohort" with a genotyping test performed within 180 days of infection were included. The 2009 WHO List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistance was used for estimating the prevalence of TDR and phylogenetic analysis for subtype determination. 189 patients with acute/recent HIV-1 infection were analyzed in 4 time periods (1997-2000, n=28; 2001-4, n=42; 2005-8, n=55 and 2009-12, n=64). The proportion of patients with acute/recent HIV-1 infection with respect to the total of newly HIV-diagnosed patients in our center increased over the time and was 2.18%, 3.82%, 4.15% and 4.55% for the 4 periods, respectively (p=0.005). The global prevalence of TDR was 9%, or 17.9%, 9.5%, 3.6% and 9.4% by study period (p=0.2). The increase in the last period was driven by protease-inhibitor and nucleoside-reverse-transcriptase-inhibitor resistance mutations while non-nucleoside-reverse-transcriptase inhibitor TDR and TDR of more than one family decreased. The overall prevalence of non-B subtypes was 11.1%, or 0%, 4.8%, 9.1% and 20.3 by study period (p=0.01). B/F recombinants, B/G recombinants and subtype F emerged in the last period. We also noticed an increase in the number of immigrant patients (p=0.052). The proportion of men-who-have-sex-with-men (MSM) among patients with acute/recent HIV-1 infection increased over the time (p=0.04). The overall prevalence of TDR in patients with acute/recent HIV-1 infection in Barcelona was 9%, and it has stayed relatively stable in recent years. Non-B subtypes and immigrants proportions progressively increased.

  11. Vaccination Against Hepatitis B Virus (HBV) in HIV-1-Infected Patients With Isolated Anti-HBV Core Antibody: The ANRS HB EP03 CISOVAC Prospective Study.

    PubMed

    Piroth, Lionel; Launay, Odile; Michel, Marie-Louise; Bourredjem, Abderrahmane; Miailhes, Patrick; Ajana, Faiza; Chirouze, Catherine; Zucman, David; Wendling, Marie-Josee; Nazzal, Dani; Carrat, Fabrice; Rey, David; Binquet, Christine

    2016-06-01

    Although an isolated anti-hepatitis B virus (HBV) core antibody (anti-HBc) serological profile is frequent in human immunodeficiency virus (HIV)-infected patients, data on HBV vaccination in these patients are scarce. A prospective multicenter study was conducted to assess the immunogenicity of HBV vaccination in 54 patients with an isolated anti-HBc profile and undetectable HIV load. They were vaccinated with 1 dose (20 µg) of recombinant HBV vaccine. Those with an anti-HBV surface antibody (anti-HBs) level of <10 mIU/mL 4 weeks after vaccination received 3 additional double doses (40 µg) at weeks 5, 9, and 24. At week 4, 25 patients (46%) were responders. Only the ratio of CD4(+) T cells to CD8(+) T cells was associated with this response in multivariate analysis (odds ratio for +0.1, 1.32; 95% confidence interval, 1.07-1.63; P = .008). At week 28 and month 18, 58% of these patients (14 of 24) and 50% (10 of 20), respectively, maintained anti-HBs level of ≥10 mIU/mL.Among nonresponding patients at week 4, who received further vaccinations, 89% (24 of 27) and 81% (21 of 26) had an anti-HBs level of ≥10 mIU/mL at week 28 and month 18, respectively. The preS2-specific interferon γ T-cell response increased between week 0 and week 28 in patients who finally responded to reinforced vaccination (P = .03). All of the patients with an isolated anti-HBc profile who did not have an anti-HBs titer of >100 mIU/mL 4 weeks after a single recall dose of HBV vaccine should be further vaccinated with a reinforced triple double-dose scheme. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  12. Improving outcomes for patients receiving transarterial chemoembolization for hepatocellular carcinoma.

    PubMed

    McCurdy, Heather M

    2013-01-01

    Hepatocellular carcinoma is a cancer with increasing incidence in the veteran population. This type of cancer can be treated with transarterial chemoembolization, an invasive procedure performed by specially trained interventional radiologists. The most common serious complications are liver failure, sepsis secondary to ischemic cholecystitis or liver abscess, gastrointestinal bleeding, and death. However, nursing staff and physicians often have little or no experience in caring for patients in the hospital who have had this procedure. Patient safety can be threatened by this lack of knowledge. Sources of threat to patient safety are described by the Institute of Medicine as falling into 4 categories: management, workforce, work processes, and organizational culture. To promote patient safety, defenses need to be deployed to address each category. In this article, the author provides a case example, describes threats to the patient's safety, and describes a plan to improve the care of all patients undergoing this procedure.

  13. Peripheral neuropathy in patients with gynecologic cancer receiving chemotherapy: patient reports and provider assessments.

    PubMed

    Kiser, Deleslie W; Greer, Tara B; Wilmoth, Margaret C; Dmochowski, Jacek; Naumann, R Wendel

    2010-11-01

    To analyze the incidence of chemotherapy-induced neuropathy in a set of patients with gynecologic cancer who were treated with known neurotoxic agents, to identify correlative factors related to patients' experience of neuropathy, and to analyze providers' assessment and treatment of neuropathy. Observational descriptive study of patient-reported neuropathy using a retrospective chart analysis. A hospital-based outpatient infusion center in the southeastern United States. A convenience sample of 171 patients with gynecologic cancer for a total of 302 chemotherapy treatments. A mixed model and compound symmetry covariance matrix was used to adjust for correlations between neuropathy treatment scores and patients who completed more than one chemotherapy cycle. Backward elimination method was used to determine the final model. Functional Assessment of Cancer Treatment/Gynecologic Oncology Group-Neuropathy Treatment scores, patients' demographic information, past medical history, and chemotherapy history. Patients who were physically shorter and heavier than the average population had the highest rating of neuropathy. Patients who were treated with nontaxane and platinum therapies had less neuropathy than patients who were treated with first-line taxanes and platinums. Neuropathy was noted by providers early in the course of treatment, and providers' grading was consistent with the patients' scoring. First-line treatments for gynecologic malignancies resulted in the highest neuropathy scores; however, patients who had received previous treatment with taxane and platinum therapies had lower neuropathy scores than patients currently receiving taxanes and platinums, suggesting that neuropathy improved after completion of first-line therapy and that second-line therapies were not necessarily correlative with worsening scores. Nurses must educate patients about symptoms of neuropathy and the need to report symptoms. Nurses must recognize patients at highest risk for

  14. Acupuncture Safety in Patients Receiving Anticoagulants: A Systematic Review

    PubMed Central

    McCulloch, Michael; Nachat, Arian; Schwartz, Jonathan; Casella-Gordon, Vicki; Cook, Joseph

    2015-01-01

    Introduction: Theoretically, acupuncture in anticoagulated patients could increase bleeding risk. However, precise estimates of bleeding complication rates from acupuncture in anticoagulated patients have not been systematically examined. Objective: To critically evaluate evidence for safety of acupuncture in anticoagulated patients. Methods: We searched PubMed, EMBASE, the Physiotherapy Evidence Database, and Google Scholar. Results: Of 39 potentially relevant citations, 11 met inclusion criteria: 2 randomized trials, 4 case series, and 5 case reports. Seven provided reporting quality sufficient to assess acupuncture safety in 384 anticoagulated patients (3974 treatments). Minor-moderate bleeding related to acupuncture in an anticoagulated patient occurred in one case: a large hip hematoma, managed with vitamin K reversal and warfarin discontinuation following reevaluation of its medical justification. Blood-spot bleeding, typical for any needling/injection and controlled with pressure/cotton, occurred in 51 (14.6%) of 350 treatments among a case series of 229 patients. Bleeding deemed unrelated to acupuncture during anticoagulation, and more likely resulting from inappropriately deep needling damaging tissue or from complex anticoagulation regimens, occurred in 5 patients. No bleeding was reported in 2 studies (74 anticoagulated patients): 1 case report and 1 randomized trial prospectively monitoring acupuncture-associated bleeding as an explicit end point. Altogether, 1 moderate bleeding event occurred in 3974 treatments (0.003%). Conclusion: Acupuncture appears to be safe in anticoagulated patients, assuming appropriate needling location and depth. The observed 0.003% complication rate is lower than the previously reported 12.3% following hip/knee replacement in a randomized trial of 27,360 anticoagulated patients, and 6% following acupuncture in a prospective study of 229,230 all-type patients. Prospective trials would help confirm our findings. PMID:25432001

  15. Faster assessment of patients receiving unnecessary thyroid treatment: concise communication

    SciTech Connect

    Stoffer, S.S.; Szpunar, W.E.; Meier, D.A.

    1983-02-01

    Forty-five consecutive patients on thyroid hormone treatment without obvious indication were evaluated. Twenty-five of these cases were found to have no evidence of thyroid disease. Biochemical testing was not helpful in making the diagnosis of hypothyroidism in the majority of thyroid-treated hypothyroid patients. Normal technetium images were obtained in 25 patients, 22 of which had no thyroid disease. In contrast, abnormal technetium images were obtained in 20 patients, 16 of whom were thought to be hypothyroid, and one of whom developed a goiter within 2 mo after discontinuing levothyroxine. The use of technetium imaging seems useful for the rapid (20 min) evaluation of those patients likely to benefit from discontinuing thyroid medication.

  16. Patient satisfaction in urology: effects of hospital characteristics, demographic data and patients' perceptions of received care.

    PubMed

    Schoenfelder, Tonio; Schaal, Tom; Klewer, Joerg; Kugler, Joachim

    2014-09-06

    To identify factors that are significantly associated with patient satisfaction in urology and to assess the extent to which satisfaction ratings might be related to hospital and patient characteristics. Data used in this study were obtained from 1040 randomly selected urology patients discharged from nine hospitals who responded to a mailed survey. Bivariate and multivariate techniques were used to reveal relations between patient assessments of received care, hospital and patient characteristics. Bivariate analysis showed a strong association between satisfaction scores and length of stay, provider status, work load of nurses and hospital size, with weaker findings pertaining to type of hospital (teaching versus non-teaching) and patient demographics. The multivariate analysis identified nine vari­ables which are associated with overall satisfaction. Strong factors were treatment outcome, the interper­sonal manner of medical practitioners and nurses, as well as hotel aspects like accommodation and quality of food. Variables reflecting information receiving about the undergoing treatment were not found to have a significant influence on patient satisfaction. This study identified variables that are related to satisfaction in a urological setting and de­livers information about aspects of the hospital stay that are not perceived as relevant by patients. These findings support healthcare professionals with valuable information to meet needs and preferences of pa­tients in urology.

  17. Hepatic safety of maraviroc in HIV-1-infected patients with hepatitis C and/or B co-infection. The Maraviroc Cohort Spanish Group.

    PubMed

    Crespo, Manuel; Navarro, Jordi; Moreno, Santiago; Sanz, Jesus; Márquez, Manuel; Zamora, Javier; Ocampo, Antonio; Iribaren, José A; Rivero, Antonio; Llibre, Josep M

    2017-10-01

    Limited data is available regarding the hepatic safety of maraviroc in patients co-infected with HIV and HCV and/or HBV. Our objective was to compare the hepatic safety profile and fibrosis progression in HIV-mono-infected patients and co-infected with HCV and/or HBV treated with maraviroc. Retrospective multicentre cohort study of HIV-infected patients receiving treatment with a maraviroc-containing regimen in 27 hospitals in Spain. A total of 667 patients were analyzed, of whom 313 were co-infected with HCV (n=282), HBV (n=14), or both (n=17). Maraviroc main indications were salvage therapy (52%) and drug toxicity (20%). Grade 3-4 hypertransaminasaemia (AST/ALT >5 times ULN) per 100 patient-years of maraviroc exposure, was 5.84 (95% CI, 4.04-8.16) and 1.23 (95% CI, 0.56-2.33) in co-infected and HIV-mono-infected patients, respectively (incidence rate ratio, 4.77; 95% CI, 2.35-10.5). However, the degree of aminotransferase abnormalities remained stable throughout the study in both groups, and no significant between-group differences were seen in the cumulative proportion of patients showing an increase in AST/ALT levels greater than 3.5 times baseline levels. No between-group differences were seen in liver fibrosis over time. With a maraviroc median exposure of 20 months (IQR, 12-41), two patients (0.3%) discontinued maraviroc because of grade 4 hepatitis, and other 2 died due to complications associated to end-stage-liver disease. Maraviroc-containing regimens showed a low incidence of hepatitis in a large Spanish cohort of HIV-infected patients, including more than 300 patients co-infected with HCV and/or HBV. Co-infection did not influence the maximum liver enzyme level or the fibrosis progression throughout the study. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  18. Promoting effective communication for patients receiving mechanical ventilation.

    PubMed

    Grossbach, Irene; Stranberg, Sarah; Chlan, Linda

    2011-06-01

    Communicating effectively with ventilator-dependent patients is essential so that various basic physiological and psychological needs can be conveyed and decisions, wishes, and desires about the plan of care and end-of-life decision making can be expressed. Numerous methods can be used to communicate, including gestures, head nods, mouthing of words, writing, use of letter/picture boards and common words or phrases tailored to meet individualized patients' needs. High-tech alternative communication devices are available for more complex cases. Various options for patients with a tracheostomy tube include partial or total cuff deflation and use of a speaking valve. It is important for nurses to assess communication needs; identify appropriate alternative communication strategies; create a customized care plan with the patient, the patient's family, and other team members; ensure that the care plan is visible and accessible to all staff interacting with the patient; and continue to collaborate with colleagues from all disciplines to promote effective communication with nonvocal patients.

  19. Nursing management of the nonhospitalized patient receiving recombinant interleukin-2.

    PubMed

    Viele, C S; Moran, T A

    1993-08-01

    Clinical trials have demonstrated that rIL-2 can be safely administered in an outpatient setting. A thorough nursing assessment ensures patient safety and effective toxicity management. Because it is becoming more economically advantageous to treat patients on an outpatient basis, nurses will need to become involved in all aspects of managed care. Outpatient administration of rIL-2 challenges nurses to be both technologically expert and clinically proficient.

  20. Immune reconstitution in severely immunosuppressed antiretroviral-naive HIV type 1-infected patients using a nonnucleoside reverse transcriptase inhibitor-based or a boosted protease inhibitor-based antiretroviral regimen: three-year results (The Advanz Trial): a randomized, controlled trial.

    PubMed

    Miró, José M; Manzardo, Christian; Pich, Judith; Domingo, Pere; Ferrer, Elena; Arribas, José R; Ribera, Esteban; Arrizabalaga, Julio; Loncá, Montserrat; Cruceta, Anna; de Lazzari, Elisa; Fuster, Montserrat; Podzamczer, Daniel; Plana, Montserrat; Gatell, José M

    2010-07-01

    Late diagnosis of HIV-1 infection is quite frequent in Western countries. Very few randomized clinical trials to determine the best antiretroviral treatment in patients with advanced HIV-1 infection have been performed. To compare immune reconstitution in two groups of very immunosuppressed (less than 100 CD4(+) cells/microl), antiretroviral-naive HIV-1-infected adults, 65 patients were randomly assigned in a 1:1 ratio to receive zidovudine + lamivudine + efavirenz (group A, 34 patients) or zidovudine + lamivudine + ritonavir-boosted indinavir (group B, 31 patients). The median (interquartile range) CD4(+) cell increase after 12 and 36 months was +199 (101, 258) and +299 (170, 464) cells/microl in the efavirenz arm and +136 (57, 235) and +228 (119, 465) cells/microl in the ritonavir-boosted indinavir arm (p > 0.05 for all time points). The proportion (95% confidence interval) of patients achieving HIV-1 RNA levels under 50 copies/ml was significantly greater in the efavirenz arm at 3 years by the intention-to-treat analysis [59% (41%, 75%) vs. 23% (10%, 41%)], whereas no differences were found in the on-treatment analysis. Immune activation (CD8(+)CD38(+) and CD8(+)CD38DR(+) T cells) was significantly lower for the efavirenz arm from month 6 to month 24. Adverse events were more frequent in the ritonavir-boosted indinavir arm. Almost all cases of disease progression and death were observed in the first year of treatment, with no significant differences between the two arms (p = 0.79 by the log-rank test). At 1 and 3 years, the immune reconstitution induced by an efavirenz-based regimen in very immunosuppressed patients was at least as potent as that induced by a ritonavir-boosted protease inhibitor-based antiretroviral regimen.

  1. Muscle strength in breast cancer patients receiving different treatment regimes

    PubMed Central

    Klassen, Oliver; Schmidt, Martina E.; Ulrich, Cornelia M.; Schneeweiss, Andreas; Potthoff, Karin; Steindorf, Karen

    2016-01-01

    Abstract Background Muscle dysfunction and sarcopenia have been associated with poor performance status, an increased mortality risk, and greater side effects in oncologic patients. However, little is known about how performance is affected by cancer therapy. We investigated muscle strength in breast cancer patients in different adjuvant treatment settings and also compared it with data from healthy individuals. Methods Breast cancer patients (N = 255) from two randomized controlled exercise trials, staged 0–III and aged 54.4 ± 9.4 years, were categorized into four groups according to their treatment status. In a cross‐sectional design, muscle function was assessed bilaterally by isokinetic dynamometry (0°, 60°, 180°/s) as maximal voluntary isometric contraction (MVIC) and maximal isokinetic peak torque (MIPT) in shoulder rotators and knee flexors and extensors. Additionally, muscular fatigue index (FI%) and shoulder flexibility were evaluated. Healthy women (N = 26), aged 53.3 ± 9.8 years, were tested using the same method. Analysis of covariance was used to estimate the impact of different cancer treatments on skeletal muscle function with adjustment for various clinical and socio‐demographic factors. Results Consistently, lower muscle strength was measured in shoulder and knee strength in patients after chemotherapy. On average, patients had up to 25% lower strength in lower extremities and 12–16% in upper extremities in MVIC and MIPT during cancer treatment compared with healthy women. No substantial difference between patient groups in shoulder strength, but significantly lower shoulder flexibility in patients with radical mastectomy was measured. Chemotherapy‐treated patients had consistently higher FI%. No serious adverse events were reported. Conclusions Breast cancer patients showed markedly impaired muscle strength and joint dysfunctions before and after anticancer treatment. The significant differences between patients

  2. Reduced Need for Rescue Antiemetics and Improved Capacity to Eat in Patients Receiving Acupuncture Compared to Patients Receiving Sham Acupuncture or Standard Care during Radiotherapy

    PubMed Central

    Steineck, Gunnar; Börjeson, Sussanne

    2017-01-01

    Objective. To evaluate if consumption of emesis-related care and eating capacity differed between patients receiving verum acupuncture, sham acupuncture, or standard care only during radiotherapy. Methods. Patients were randomized to verum (n = 100) or sham (n = 100) acupuncture (telescopic blunt sham needle) (median 12 sessions) and registered daily their consumption of antiemetics and eating capacity. A standard care group (n = 62) received standard care only and delivered these data once. Results. More patients in the verum (n = 73 of 89 patients still undergoing radiotherapy; 82%, Relative Risk (RR) 1.23, 95% Confidence Interval (CI) 1.01–1.50) and the sham acupuncture group (n = 79 of 95; 83%, RR 1.24, CI 1.03–1.52) did not need any antiemetic medications, as compared to the standard care group (n = 42 out of 63; 67%) after receiving 27 Gray dose of radiotherapy. More patients in the verum (n = 50 of 89; 56%, RR 1.78, CI 1.31–2.42) and the sham acupuncture group (n = 58 of 94 answering patients; 62%, RR 1.83, CI 1.20–2.80) were capable of eating as usual, compared to the standard care group (n = 20 of 63; 39%). Conclusion. Patients receiving acupuncture had lower consumption of antiemetics and better eating capacity than patients receiving standard antiemetic care, plausible by nonspecific effects of the extra care during acupuncture. PMID:28270851

  3. Drug utilisation study in patients receiving antiepileptic drugs in Colombia.

    PubMed

    Machado-Alba, J E; Calvo-Torres, L F; García-Betancur, S; Aguirre-Novoa, A; Bañol-Giraldo, A M

    2016-03-01

    This study examines the indications according to which antiepileptic drugs are prescribed and used in a population of patients enrolled in the Colombian national health system (SGSSS). Retrospective cross-sectional study. From the pool of individuals in 34 Colombian cities who used antiepileptic drugs between 18 July, 2013 and 31 August, 2014 during a period of no less than 12 months, we obtained a random sample stratified by city. Socio-demographic, pharmacological and comorbidity variables were analysed. Continuous and categorical variables were compared, and logistic regression models were used. Our patient total was 373 patients, with 197 women (52.1%) and a mean age of 41.9 ± 21.7 years; 65.4% of the patients were treated with monotherapy. The most frequently used drugs were valproic acid (53.1%) and carbamazepine (33.2%). Epilepsy was the most frequent indication (n=178; 47.7%); however, 52.3% of the patients were prescribed antiepileptics for different indications, especially neuropathic pain (26.8%), affective disorders (14.2%) and migraine prophylaxis (12.3%). A total of 81 patients with epilepsy (46.6%) displayed good seizure control while another 25 (14.4%) had drug-resistant epilepsy. In the multivariate analysis, medication adherence was associated with a lower risk of treatment failure in patients with epilepsy (OR: 0.27; 95%CI, 0.11-0.67). In Colombia, antiepileptic drugs are being used for indications other than those originally intended. Monotherapy is the most commonly used treatment approach, together with the use of classic antiepileptic drugs. Copyright © 2015 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  4. [Quality of care in diabetic patients receiving pharmacologic treatment].

    PubMed

    Lombraña, María A; Capetta, María E; Ugarte, Alejandro; Correa, Viviana; Giganti, Jorge; Saubidet, Cristian Lopez; Stryjewski, Martin E

    2007-01-01

    Diabetes mellitus is a chronic disease with an increasing prevalence. Appropriate treatment of the disease and prevention of chronic complications reduce morbidity and mortality in a cost-effective manner. These actions should be measured through the use of validated indicators for quality of care. The goal of this study was to assess the quality of care in diabetic patients under pharmacologic treatment in a private university hospital. A retrospective study was conducted in adult patients who bought insulin or oral hypoglycemic agents during a 3 month period; demographic and clinical data were obtained for 12 consecutive months following the buying period. The study included 305 adult patients; most were males (60%), with type 2 diabetes (95%), and using oral hipoglycemic agents (86%). Control of blood pressure was registered in 80%, foot exam in 5%, eye exam in 27%, HbA1C blood level in 85%, complete lipid profile in 82%, microalbuminuria in 27% and creatinine clearance in 22% of patients, respectively. Mean values were HbA1C 7.1(+/- 1.6)%, and < or = 7% in 66%, LDL 113 (+/- 33.6) mg/dl and <100 mg/dl in 30%, BP 136-79 mm Hg and < 130-80 mm Hg in 46% of patients, respectively. This study emphasizes the need for quality of care assessment through validated indicators and points out the aspects that should be improved within a health care system.

  5. Aerosol therapy in patients receiving noninvasive positive pressure ventilation.

    PubMed

    Dhand, Rajiv

    2012-04-01

    In selected patients, noninvasive positive pressure ventilation (NIPPV) with a facemask is now commonly employed as the first choice for providing mechanical ventilation in the intensive care unit (ICU). Aerosol therapy for treatment of acute or acute-on-chronic respiratory failure in this setting may be delivered by pressurized metered-dose inhaler (pMDI) with a chamber spacer and facemask or nebulizer and facemask. This article reviews the host of factors influencing aerosol delivery with these devices during NIPPV. These factors include (1) the type of ventilator, (2) mode of ventilation, (3) circuit conditions, (4) type of interface, (5) type of aerosol generator, (6) drug-related factors, (7) breathing parameters, and (8) patient-related factors. Despite the impediments to efficient aerosol delivery because of continuous gas flow, high inspiratory flow rates, air leaks, circuit humidity, and patient-ventilator asynchrony, significant therapeutic effects are achieved after inhaled bronchodilator administration to patients with asthma and chronic obstructive pulmonary disease. Similarly to invasive mechanical ventilation, careful attention to the technique of drug administration is required to optimize therapeutic effects of inhaled therapies during NIPPV. Assessment of the patient's ability to tolerate a facemask, the level of respiratory distress, hemodynamic status, and synchronization of aerosol generation with inspiratory airflow are important factors contributing to the success of aerosol delivery during NIPPV. Further research into novel delivery methods, such as the use of NIPPV with nasal cannulae, could enhance the efficiency, ease of use, and reproducibility of inhalation therapy during noninvasive ventilation.

  6. Patients Receiving Prebiotics and Probiotics Before Liver Transplantation Develop Fewer Infections Than Controls: A Systematic Review and Meta-Analysis.

    PubMed

    Sawas, Tarek; Al Halabi, Shadi; Hernaez, Ruben; Carey, William D; Cho, Won Kyoo

    2015-09-01

    Among patients who have received liver transplants, infections increase morbidity and mortality and prolong hospital stays. Administration of antibiotics and surgical trauma create intestinal barrier dysfunction and microbial imbalances that allow enteric bacteria to translocate to the blood. Probiotics are believed to prevent bacterial translocation by stabilizing the intestinal barrier and stimulating proliferation of the intestinal epithelium, mucus secretion, and motility. We performed a meta-analysis to determine the effects of probiotics on infections in patients receiving liver transplants. We searched PubMed and EMBASE for controlled trials that evaluated the effects of prebiotics and probiotics on infections in patients who underwent liver transplantation. Heterogeneity was analyzed by the Cochran Q statistic. Pooled Mantel-Haenszel relative risks were calculated with a fixed-effects model. We identified 4 controlled studies, comprising 246 participants (123 received probiotics, 123 served as controls), for inclusion in the meta-analysis. In these studies, the intervention groups received enteric nutrition and fiber (prebiotics) with probiotics, and the control groups received only enteric nutrition and fiber without probiotics. The infection rate was 7% in groups that received probiotics vs 35% in control groups (relative risk [RR], 0.21; 95% confidence interval [CI], 0.11-0.41; P = .001). The number needed to treat to prevent 1 infection was 3.6. In subgroup analyses, only 2% of subjects in the probiotic groups developed urinary tract infections, compared with 16% of controls (RR, 0.14; 95% CI, 0.04-0.47; P < .001); only 2% of subjects in the probiotic groups developed intra-abdominal infections, compared with 11% of controls (RR, 0.27; 95% CI, 0.09-0.78; P = .02). Subjects receiving probiotics also had shorter stays in the hospital than controls (mean difference, 1.41 d; P < .001), as well as in the intensive care unit (mean difference, 1.41 d; P

  7. Serum ferritin concentration in patients receiving maintenance hemodialysis.

    PubMed

    Lynn, K L; Mitchell, T R; Shepperd, J

    1980-09-01

    Studies in 144 patients on maintenace hemodialysis have shown that serum ferritin concentration is influenced by the period the patient has been on dialysis, the presence of liver disease and to some extent the underlying diagnosis. It was observed that parenteral iron therapy could still produce an increase in hemoglobin concentration when the serum ferritin was as high as 60--55 micrograms/l. This suggests that the target serum ferritin, whatever the route of iron replacement, should be at least 55 micrograms/l. The higher levels of ferritin at which an increase in hemoglobin concentration can occur, together with the variable increment in serum ferritin after parenteral iron, indicates that the simple relationship between serum ferritin and marrow iron stores may be distrubed in some patients.

  8. Metabolic Acidosis in a Pediatric Patient Receiving Topiramate

    PubMed Central

    Malik, Razia; Iacoune, John

    2003-01-01

    Topiramate is an anticonvulsant that is labeled for the management of several seizure types in children >2 years of age. With the exception of cognitive dysfunction, nephrolithiasis, weight loss, and paresthesia, adverse effects in children are similar to other those noted with other anticonvulsants. We describe a 33-month-old child with complex partial seizures and secondary generalization who received topiramate 45 mg orally twice daily (6.2 mg/kg/d) for approximately 4 weeks before admission. He developed asymptomatic metabolic acidosis that was evidenced by a decrease in HCO3−, which was unresponsive to treatment with sodium bicarbonate. The child was weaned off topiramate and the metabolic acidosis resolved 48 hours after its discontinuation. PMID:23118685

  9. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A treatment

    USDA-ARS?s Scientific Manuscript database

    We sought to determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. DESIGN: Randomized, controlled, double-masked trial of 225 nonsmoking patients, aged 18 to 60 years, evaluated over a 4-year interval. Patients received ...

  10. Visceral leishmaniasis in a rheumatoid arthritis patient receiving methotrexate.

    PubMed

    Reina, Delia; Cerdà, Dacia; Güell, Elena; Martínez Montauti, Joaquín; Pineda, Antonio; Corominas, Hèctor

    2016-08-11

    Patients with rheumatoid arthritis (RA) treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis. As L. infantum is endemic in the Mediterranean region, it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia. An early diagnosis based on a high suspicion can prevent a fatal outcome. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  11. Cross-resistance to elvitegravir and dolutegravir in 502 patients failing on raltegravir: a French national study of raltegravir-experienced HIV-1-infected patients.

    PubMed

    Fourati, Slim; Charpentier, Charlotte; Amiel, Corinne; Morand-Joubert, Laurence; Reigadas, Sandrine; Trabaud, Mary-Anne; Delaugerre, Constance; Nicot, Florence; Rodallec, Audrey; Maillard, Anne; Mirand, Audrey; Jeulin, Hélène; Montès, Brigitte; Barin, Francis; Bettinger, Dominique; Le Guillou-Guillemette, Hélène; Vallet, Sophie; Signori-Schmuck, Anne; Descamps, Diane; Calvez, Vincent; Flandre, Philippe; Marcelin, Anne-Genevieve

    2015-05-01

    The objectives of this study were to determine the prevalence and patterns of resistance to integrase strand transfer inhibitors (INSTIs) in patients experiencing virological failure on raltegravir-based ART and the impact on susceptibility to INSTIs (raltegravir, elvitegravir and dolutegravir). Data were collected from 502 treatment-experienced patients failing a raltegravir-containing regimen in a multicentre study. Reverse transcriptase, protease and integrase were sequenced at failure for each patient. INSTI resistance-associated mutations investigated were those included in the last ANRS genotypic algorithm (v23). Among the 502 patients, at failure, median baseline HIV-1 RNA (viral load) was 2.9 log10 copies/mL. Patients had been previously exposed to a median of five NRTIs, one NNRTI and three PIs. Seventy-one percent harboured HIV-1 subtype B and the most frequent non-B subtype was CRF02_AG (13.3%). The most frequent mutations observed were N155H/S (19.1%), Q148G/H/K/R (15.4%) and Y143C/G/H/R/S (6.7%). At failure, viruses were considered as fully susceptible to all INSTIs in 61.0% of cases, whilst 38.6% were considered as resistant to raltegravir, 34.9% to elvitegravir and 13.9% to dolutegravir. In the case of resistance to raltegravir, viruses were considered as susceptible to elvitegravir in 11% and to dolutegravir in 64% of cases. High HIV-1 viral load at failure (P < 0.001) and low genotypic sensitivity score of the associated treatment with raltegravir (P < 0.001) were associated with the presence of raltegravir-associated mutations at failure. Q148 mutations were selected more frequently in B subtypes versus non-B subtypes (P = 0.004). This study shows that a high proportion of viruses remain susceptible to dolutegravir in the case of failure on a raltegravir-containing regimen. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions

  12. Do heroin overdose patients require observation after receiving naloxone?

    PubMed

    Willman, Michael W; Liss, David B; Schwarz, Evan S; Mullins, Michael E

    2017-02-01

    Heroin use in the US has exploded in recent years, and heroin overdoses requiring naloxone are very common. After awakening, some heroin users refuse further treatment or transport to the hospital. These patients may be at risk for recurrent respiratory depression or pulmonary edema. In those transported to the emergency department, the duration of the observation period is controversial. Additionally, non-medical first responders and lay bystanders can administer naloxone for heroin and opioid overdoses. There are concerns about the outcomes and safety of this practice as well. To search the medical literature related to the following questions: (1) What are the medical risks to a heroin user who refuses ambulance transport after naloxone? (2) If the heroin user is treated in the emergency department with naloxone, how long must they be observed prior to discharge? (3) How effective in heroin users is naloxone administered by first responders and bystanders? Are there risks associated with naloxone distribution programs? We searched PubMed and GoogleScholar with search terms related to each of the questions listed above. The search was limited to English language and excluded patents and citations. The search was last updated on September 31, 2016. The articles found were reviewed for relevance to our objective questions. Eight out of 1020 citations were relevant to the first 2 questions, 5 of 707 were relevant to the third question and 15 of 287 were relevant to the fourth question. In the prehospital environment, does a heroin user revived with naloxone always require ambulance transport and what are the medical risks if ambulance transport is refused after naloxone? The eight articles were all observational studies done either prospectively or retrospectively. Two studies focused on heroin overdoses and included 1069 patients not transported to the hospital. No deaths occurred in this group. In counting the patients from all eight studies, some of which

  13. What Do Patients Prefer? Understanding Patient Perspectives on Receiving a New Breast Cancer Diagnosis.

    PubMed

    Attai, Deanna J; Hampton, Regina; Staley, Alicia C; Borgert, Andrew; Landercasper, Jeffrey

    2016-10-01

    There is variability in physician practice regarding delivery method and timeliness of test results to cancer patients. Our aim was to survey patients to determine if there was a difference between actual and preferred care for disclosure of test results. A de-identified survey was distributed to online cancer support groups to query patients about their experience regarding communication of cancer testing and timeliness. Analyses of the differences between actual and preferred communication and wait times were performed. Overall, 1000 patients completed the survey. The analysis herein was restricted to 784 breast cancer survivors. Survey responders were predominately White (non-Hispanic; 89 %), college educated (78 %), and media 'savvy' (online medical media usage; 97 %). Differences between actual and preferred care were identified for the domains of mode of communication and wait times for initial breast cancer diagnostic biopsies and other tests. A total of 309 (39 %) of 784 patients received face-to-face communication for a new cancer diagnosis, with 394 (50 %) patients preferring this option (p < 0.0001). In addition, 315 (40 %) of 784 patients received their cancer biopsy result within 2 days, with 646 (82 %) patients preferring this option (p < 0.0001). Differences were also identified between actual and preferred care for multiple other test types. Actual care for timeliness and modes of communication did not reflect patient-desired care. National and local initiatives to improve performance are needed. As a first step, we recommend that each patient be queried about their preference for mode of communication and timeliness, and efforts made to comply.

  14. Sex Differences in Patients Receiving Anticoagulant Therapy for Venous Thromboembolism

    PubMed Central

    Blanco-Molina, Angeles; Enea, Iolanda; Gadelha, Telma; Tufano, Antonella; Bura-Riviere, Alessandra; Di Micco, Pierpaolo; Bounameaux, Henri; González, José; Villalta, Jaume; Monreal, Manuel

    2014-01-01

    Abstract In patients with venous thromboembolism (VTE), the outcome during the course of anticoagulant therapy may differ according to the patient’s sex. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of VTE recurrences, major bleeding, and mortality due to these events according to sex. As of August 2013, 47,499 patients were enrolled in RIETE, of whom 24,280 (51%) were women. Women were older, more likely presented with pulmonary embolism (PE), and were more likely to have recent immobilization but less likely to have cancer than men. During the course of anticoagulation (mean duration: 253 d), 659 patients developed recurrent deep vein thrombosis (DVT), 576 recurrent PE, 1368 bled, and 4506 died. Compared with men, women had a lower rate of DVT recurrences (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.67–0.91), a similar rate of PE recurrences (HR: 0.98; 95% CI: 0.83–1.15), a higher rate of major bleeding (HR: 1.21; 95% CI: 1.09–1.35), and higher mortality due to PE (HR: 1.24; 95% CI: 1.04–1.47). On multivariable analysis, any influence of sex on the risk for recurrent DVT (HR: 0.88; 95% CI: 0.75–1.03), major bleeding (HR: 1.10; 95% CI: 0.98–1.24), or fatal PE (HR: 1.01; 95% CI: 0.84–1.22) was no longer statistically significant. In conclusion, women had fewer DVT recurrences and more bleeds than men during the course of anticoagulation. These differences were not due to sex, but very likely to other patient characteristics more common in female patients and differences in treatment choice. PMID:25398066

  15. Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis

    PubMed Central

    Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

    2017-01-01

    Aims: To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis. Patients and methods: A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated. Results: Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables. Conclusion: In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy. PMID:28261338

  16. Point-of-care lactate testing predicts mortality of severe sepsis in a predominantly HIV type 1-infected patient population in Uganda.

    PubMed

    Moore, Christopher C; Jacob, Shevin T; Pinkerton, Relana; Meya, David B; Mayanja-Kizza, Harriet; Reynolds, Steven J; Scheld, W Michael

    2008-01-15

    Prediction of mortality may improve management and outcomes of patients with sepsis in resource-limited settings. Therefore, we evaluated the ability of a hand-held portable whole-blood lactate (PWBL) analyzer to predict mortality of patients who are admitted to the hospital with severe sepsis. A prospective observational study enrolled 253 patients at a national referral hospital in Uganda. Inclusion criteria required (1) >or=2 systemic inflammatory response syndrome criteria or thermodysregulation, (2) hypotension, and (3) suspected infection. A subset of 72 patients had PWBL and standard laboratory serum lactate measured. The primary measured outcome was in-hospital mortality. Fifty-nine (81.9%) of 72 evaluated patients were infected with human immunodeficiency virus type 1. The in-hospital mortality rate was 25.7% (18 of 70), and the in- and outpatient mortality at 30 days was 41.6% (30 of 72). PWBL was positively associated with in-hospital but not outpatient mortality (P=.001). The receiver operating characteristic area under the curve for PWBL was 0.81 (P=.081). The optimal PWBL concentration for predicting in-hospital mortality (sensitivity, 88.3%; specificity, 71.2%) was >or=4.0 mmol/L. Patients with a PWBL concentration >or=4.0 mmol/L died while in the hospital substantially more often (50.0%) than did those with a PWBL concentration <4.0 mmol/L (7.5%) (odds ratio, 12.3; 95% confidence interval, 3.5-48.9; [P=.001). Standard laboratory serum lactate results were inconsistent and less predictive of mortality than were those of PWBL in a multiple logistic regression model. A PWBL concentration >or=4.0 mmol/L predicts with 81% accuracy a 7-fold higher mortality of patients with sepsis than does a PWBL concentration <4.0 mmol/L. PWBL testing would be useful in places where clinical decisions are limited by lack of laboratory infrastructure and poor reliability.

  17. Probiotics Differently Affect Gut-Associated Lymphoid Tissue Indolamine-2,3-Dioxygenase mRNA and Cerebrospinal Fluid Neopterin Levels in Antiretroviral-Treated HIV-1 Infected Patients: A Pilot Study

    PubMed Central

    Scagnolari, Carolina; Corano Scheri, Giuseppe; Selvaggi, Carla; Schietroma, Ivan; Najafi Fard, Saeid; Mastrangelo, Andrea; Giustini, Noemi; Serafino, Sara; Pinacchio, Claudia; Pavone, Paolo; Fanello, Gianfranco; Ceccarelli, Giancarlo; Vullo, Vincenzo; d’Ettorre, Gabriella

    2016-01-01

    Recently the tryptophan pathway has been considered an important determinant of HIV-1 infected patients’ quality of life, due to the toxic effects of its metabolites on the central nervous system (CNS). Since the dysbiosis described in HIV-1 patients might be responsible for the microbial translocation, the chronic immune activation, and the altered utilization of tryptophan observed in these individuals, we speculated a correlation between high levels of immune activation markers in the cerebrospinal fluid (CSF) of HIV-1 infected patients and the over-expression of indolamine-2,3-dioxygenase (IDO) at the gut mucosal surface. In order to evaluate this issue, we measured the levels of neopterin in CSF, and the expression of IDO mRNA in gut-associated lymphoid tissue (GALT), in HIV-1-infected patients on effective combined antiretroviral therapy (cART), at baseline and after six months of probiotic dietary management. We found a significant reduction of neopterin and IDO mRNA levels after the supplementation with probiotic. Since the results for the use of adjunctive therapies to reduce the levels of immune activation markers in CSF have been disappointing so far, our pilot study showing the efficacy of this specific probiotic product should be followed by a larger confirmatory trial. PMID:27689995

  18. Perioperative Considerations and Management of Patients Receiving Anticoagulants

    PubMed Central

    Shaikh, Safiya Imtiaz; Kumari, R. Vasantha; Hegade, Ganapati; Marutheesh, M.

    2017-01-01

    Anticoagulants remain the primary strategy for the prevention and treatment of thrombosis. Unfractionated heparin, low molecular weight heparin (LMWH), fondaparinux, and warfarin have been studied and employed extensively with direct thrombin inhibitors typically reserved for patients with complications or those requiring interventions. Novel oral anticoagulants have emerged from clinical development and are expected to replace older agents with their ease to use and more favorable pharmacodynamic profiles. Increasingly, anesthesiologists are being requested to anesthetize patients who are on some form of anticoagulants and hence it is important to have sound understanding of pharmacology, dosing, monitoring, and toxicity of anticoagulants. We searched the online databases including PubMed Central, Cochrane, and Google Scholar using anticoagulants, perioperative management, anesthetic considerations, and LMWH as keywords for the articles published between 1994 and 2015 while writing this review. In this article, we will review the different classes of anticoagulants and how to manage them in the perioperative settings. PMID:28298749

  19. PSYCHIATRIC DISORDERS IN PATIENTS RECEIVING ANTI-TUBERCULOSIS DRUGS

    PubMed Central

    Prasad, C.E.; Krishnamurthy, Kartikeya; Murthy, K.J.R.

    1985-01-01

    SUMMARY Eleven in-patients of the hospital for Tuberculosis and Chest Diseases, Hyderabad, who presented with psychiatric symptoms resulting in maladjustment were examined and placed in different diagnostic groups. There were five psychotics and six neurotics. Out of the five psychotics, three were manic and two were depressive. Among the six neutrotics, three were depressive and one each of anxiety, obsessive compulsive and phobic neurosis. All the patients improved on withdrawal of anti-tuberculosis drugs and there was no recurrence or symptoms on reintroduction of anti-tuberculosis drugs other than isoniazid. On re-introduction of Isoniazid, symptoms recurred. The psychiatric disorders were most likely due to Isoniazid and they were neither dose nor duration related. However, Isoniazid may be readministered in the less severe forms along with appropriate drugs to control psychiatric side-effects. PMID:21927126

  20. [Assessment of cardiorespiratory functions in patients receiving suggestive psychotherapy].

    PubMed

    Klassina, S Ia; Dudnik, E N; Oshovskaia, B L; Sytin, G N; Fudin, N A; Sudakov, K V

    2009-01-01

    It is shown that suggestive psychotherapy based on verbal suggestions provides a tool for individual correction of the patient's functional state. It reduces sympathetic and promotes parasympathetic influences, decreases high initial level of psychoemotional tension, and normalizes relationship between cardiac and respiratory rhythms. Also, suggestive psychotherapy has beneficial effect on the psychological sphere and subjective feeling of well-being, reduces anxiety, strengthens the sense of confidence and hope for a cure.

  1. Vitiligo in a patient receiving infliximab for refractory ulcerative colitis.

    PubMed

    Ismail, Waleed A; Al-Enzy, Saleh A; Alsurayei, Saqer A; Ismail, Ali E

    2011-06-01

    Infliximab is a chimerical monoclonal antibody that inhibits pro-inflammatory activity of tumour-necrosis factor alpha (TNFα) and it is the primary biological agent used in the treatment of moderate-to-severe ulcerative colitis (UC). We report a case of vitiligo following infliximab administration in a patient with refractory UC. The case serves as a reminder of adverse cutaneous reactions induced by TNFα-antagonist therapy.

  2. [The development of severe methemoglobinemia in patients receiving "Almagel A"].

    PubMed

    Starkov, Iu G; Kazennov, V V; Vybornyĭ, M I; Amerov, D B; Shumkina, L V

    2014-01-01

    This clinical case and the literature review show possible development of methemoglobinemia due to the use of local anesthetics, included in drugs for the gastrointestinal diseases treatment, in particular benzocaine, which is the methaemoglobin forming agent. These drugs are common and often taken by the patients themselves without any control. The aim of our paper is to draw the attention of physicians to the risk of the widely known drug administration which can be purchased without a prescription.

  3. Dental management of patients receiving anticoagulation or antiplatelet treatment.

    PubMed

    Pototski, Mariele; Amenábar, José M

    2007-12-01

    Antiplatelet and anticoagulant agents have been extensively researched and developed as potential therapies in the prevention and management of arterial and venous thrombosis. On the other hand, antiplatelet and anticoagulant drugs have also been associated with an increase in the bleeding time and risk of postoperative hemorrhage. Because of this, some dentists still recommend the patient to stop the therapy for at least 3 days before any oral surgical procedure. However, stopping the use of these drugs exposes the patient to vascular problems, with the potential for significant morbidity. This article reviews the main antiplatelet and anticoagulant drugs in use today and explains the dental management of patients on these drugs, when subjected to minor oral surgery procedures. It can be concluded that the optimal INR value for dental surgical procedures is 2.5 because it minimizes the risk of either hemorrhage or thromboembolism. Nevertheless, minor oral surgical procedures, such as biopsies, tooth extraction and periodontal surgery, can safely be done with an INR lower than 4.0.

  4. Fertility preservation in patients receiving cyclophosphamide therapy for renal disease.

    PubMed

    Gajjar, Radha; Miller, Steven D; Meyers, Kevin E; Ginsberg, Jill P

    2015-07-01

    Cyclophosphamide continues to have an important role in the treatment of renal disease, including nephrotic syndrome and lupus nephritis, despite known complications of gonadotoxicity and potential infertility in both male and female patients. It is important that the physician recommending this therapy mitigates the effect of the drug on fertility by adhering to recommendations on dosing limits and offering fertility-preserving strategies. In addition to well-established methods, such as sperm banking and embryo cryopreservation, advances in reproductive technology have yielded strategies such as oocyte cryopreservation, resulting in more fertility-preserving options for the pediatric patient. Despite these advances, there continues to be a significant barrier to referral and access to sperm banks and fertility specialists. These issues are further complicated by ethical issues associated with the treatment of pediatric patients. In this review we explore the development of recommended dosing limits and include a discussion of the available fertility-preserving methods, strategies for increasing access to fertility specialists, and the ethical considerations facing the pediatric healthcare provider.

  5. Practical management of patients with myelofibrosis receiving ruxolitinib.

    PubMed

    Harrison, Claire; Mesa, Ruben; Ross, David; Mead, Adam; Keohane, Clodagh; Gotlib, Jason; Verstovsek, Srdan

    2013-10-01

    Myelofibrosis (MF) is characterized by bone marrow fibrosis, progressive anemia and extramedullary hematopoiesis, primarily manifested as splenomegaly. Patients also experience debilitating constitutional symptoms, including sequelae of splenomegaly, night sweats and fatigue. Ruxolitinib (INC424, INCB18424, Jakafi, Jakavi), a JAK1 and JAK2 inhibitor, was approved in November 2011 by the US FDA for the treatment of intermediate- or high-risk MF, and more recently in Europe and Canada for the treatment of MF-related splenomegaly or symptoms. These approvals were based on data from two randomized Phase III studies: COMFORT-I randomized against placebo, and COMFORT-II randomized against best available therapy. In these studies, ruxolitinib rapidly improved multiple disease manifestations of MF, reducing splenomegaly and improving quality of life of patients and potentially prolonging survival. However, as with other chemotherapies, ruxolitinib therapy is associated with some adverse events, such as anemia and thrombocytopenia. The aims of this article are to provide a brief overview of ruxolitinib therapy, to discuss some common adverse events associated with ruxolitinib therapy and to provide clinical management recommendations to maximize patients' benefit from ruxolitinib.

  6. Safety of darunavir/ritonavir (DRV/r) in HIV-1-infected DRV/r-experienced and -naïve patients: analysis of data in the real-world setting in Italy.

    PubMed

    Antinori, Andrea; Borderi, Marco; Cauda, Roberto; Bini, Teresa; Chirianni, Antonio; Squillace, Nicola; Mancusi, Daniela; Termini, Roberta

    2014-01-01

    This descriptive, non-interventional study on HIV-1-infected patients treated with DRV/r in the usual clinical setting, with a single-arm prospective observational design, collected data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in marketing authorization in usual clinical practice in Italy to evaluate efficacy and safety of DRV/r-based antiretroviral (ARV) treatment. This analysis focussed on the safety profile of DRV/r in HIV-1 infected patients. Data were analyzed from four cohorts of HIV-1-infected patients treated with DRV/r in the real-world setting, including an ARV-naïve-DRV/r-naïve cohort (Cohort 1), an ARV-experienced-DRV/r-naïve cohort (Cohort 2) and two ARV-DRV/r-experienced cohorts (Cohorts 3 and 4), one of which (Cohort 3) was from the DRV/r Early Access Program. The objective of this analysis was to examine the safety data obtained in these four cohorts in patients enrolled from June 2009 to November 2011 and observed until December 2012 or DRV/r discontinuation. Safety data from 875 patients were analyzed. DRV/r-based treatment was well tolerated, with 36.2% of patients reporting ≥1 adverse event (AE) and very few discontinuations due to study drug-related AEs (3.0% overall). The most frequent AEs were diarrhoea (2.7%), reduced bone density (2.6%) and hypercholesterolaemia (2.1%) (Table 1). Regarding metabolic parameters, levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) remained stable from baseline to the last study visit (LSV) in DRV-experienced patients and decreased in DRV-naïve patients. Blood glucose concentrations remained stable in all cohorts. Serum triglyceride and cholesterol concentrations remained stable in DRV-experienced patients but increased in naïve patients, yet were still within normal range. In HIV-1-infected patients treated with DRV/r in these settings, the tolerability profile was favourable and similar to (or better than) that reported in

  7. Unexplained diarrhoea in HIV-1 infected individuals

    PubMed Central

    2014-01-01

    Background Gastrointestinal symptoms, in particular diarrhoea, are common in non-treated HIV-1 infected individuals. Although various enteric pathogens have been implicated, the aetiology of diarrhoea remains unexplained in a large proportion of HIV-1 infected patients. Our aim is to identify the cause of diarrhoea for patients that remain negative in routine diagnostics. Methods In this study stool samples of 196 HIV-1 infected persons, including 29 persons with diarrhoea, were examined for enteropathogens and HIV-1. A search for unknown and unexpected viruses was performed using virus discovery cDNA-AFLP combined with Roche-454 sequencing (VIDISCA-454). Results HIV-1 RNA was detected in stool of 19 patients with diarrhoea (66%) compared to 75 patients (45%) without diarrhoea. In 19 of the 29 diarrhoea cases a known enteropathogen could be identified (66%). Next to these known causative agents, a range of recently identified viruses was identified via VIDISCA-454: cosavirus, Aichi virus, human gyrovirus, and non-A non-B hepatitis virus. Moreover, a novel virus was detected which was named immunodeficiency-associated stool virus (IASvirus). However, PCR based screening for these viruses showed that none of these novel viruses was associated with diarrhoea. Notably, among the 34% enteropathogen-negative cases, HIV-1 RNA shedding in stool was more frequently observed (80%) compared to enteropathogen-positive cases (47%), indicating that HIV-1 itself is the most likely candidate to be involved in diarrhoea. Conclusion Unexplained diarrhoea in HIV-1 infected patients is probably not caused by recently described or previously unknown pathogens, but it is more likely that HIV-1 itself plays a role in intestinal mucosal abnormalities which leads to diarrhoea. PMID:24410947

  8. Patients' satisfaction with information and experiences with counseling on cardiovascular medication received at the pharmacy.

    PubMed

    van Geffen, Erica C G; Philbert, Daphne; van Boheemen, Carla; van Dijk, Liset; Bos, Marieke B; Bouvy, Marcel L

    2011-06-01

    To assess the extent to which patients feel they have received enough information on cardiovascular drugs and experienced counseling at the pharmacy. In addition, to identify factors that are predictors for patient satisfaction with the information received. Fifteen community pharmacies participated. New and chronic users of cardiovascular medication received a questionnaire containing sociodemographic and health questions, a measure of satisfaction with information received (SIMS), beliefs about medication (BMQ), and frequency of pharmacy counseling. Of the 578 respondents, 335 (58%) indicated to be unsatisfied with the information received on 3 or more SIMS items. Patients' age, beliefs about medication, duration of cardiovascular treatment and use of antithrombotics predicted patients' satisfaction with information received. Two-thirds of patients reported 'never' to have experienced 5 of 8 counseling activities at the pharmacy. A considerable proportion of patients are unsatisfied with the information received on cardiovascular medication. The majority of patients have only received a limited scope of medication counseling at the pharmacy. Information and counseling should be tailored to patients' needs and concerns about cardiovascular medication and the experience patients already have with treatment. Pharmacists could enhance their role in supporting patients using cardiovascular medication. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. [Method of functional impression receiving for edentulous patients].

    PubMed

    Zhulev, E N; Manakov, A L

    2007-01-01

    150 edentulous patients (78 men and 72 women) aged from 34 to 86 were examined and prosthodontically treated according to improved method. The method of taking preliminary and final mucodynamic impressions was suggested. Contractive activity of muscle groups related to the surrounding tissues was studied in comparison with the method of F. Gerbst. Optoelectronic method was used to study 3-dimensional virtual models of gypsum casts poured from impressions made both in accordance to the regular and improved methods. Better fixation of complete dentures followed getting impressions with the help of improved method was achieved.

  10. Clinical management of patients receiving cell-based immunoregulatory therapy.

    PubMed

    Hutchinson, James A; Ahrens, Norbert; Riquelme, Paloma; Walter, Lisa; Gruber, Michael; Böger, Carsten A; Farkas, Stefan; Scherer, Marcus N; Broichhausen, Christiane; Bein, Thomas; Schlitt, Hans-J; Fändrich, Fred; Banas, Bernhard; Geissler, Edward K

    2014-09-01

    Administering immunoregulatory cells as medicinal agents is a revolutionary approach to the treatment of immunologically mediated diseases. Isolating, propagating, and modifying cells before applying them to patients allows complementation of specific cellular functions, which opens astonishing new possibilities for gain-of-function antigen-specific treatments in autoimmunity, chronic inflammatory disorders, and transplantation. This critical review presents a systematic assessment of the potential clinical risks posed by cell-based immunotherapy, focusing on treatment of renal transplant recipients with regulatory macrophages as a concrete example.

  11. Stroke rehabilitation in Fiji: are patients receiving services?

    PubMed

    Waloki, M; Roseveare, C; Tikolevu, L; Ram, S; Bissell, K

    2014-09-21

    Contexte: Hôpital national du Ministère de la santé des Fidji et services de rééducation post accident vasculaire cérébral (AVC).Objectifs: Décrire les patients admis pour AVC à l'hôpital Colonial War Memorial (CWMH) de janvier 2010 à décembre 2012 et les services de rééducation fréquentés pendant et après l'hospitalisation.Schéma: Etude rétrospective descriptive grâce aux dossiers des patients.Résultats: Sur 328 patients admis pour AVC, 54% étaient des hommes, 55% appartenaient à l'ethnie i-Taukei et 16% était âgés de <50 ans ; 75% avaient une hypertension, 41% un diabète et 37% les deux pathologies ; 23% (n = 76) sont décédés. Parmi les survivants, 58% (n = 146) ont bénéficié d'une rééducation pendant leur séjour au CWMH. Après leur sortie, 10% (n = 26) ont bénéficié d'une rééducation à l'hôpital national de rééducation et six ont bénéficié de l'aide de rééducateurs communautaires. Un peu plus de la moitié des survivants (52%) sont restés au CWMH moins d'une semaine (séjour médian 6 jours ; IQR 4–11).Conclusion: La durée de séjour et l'accès à la rééducation ont été insuffisants pour plus de la moitié des survivants d'AVC. Après leur sortie, très peu ont eu accès aux services de rééducation disponibles du Ministère de la santé. Il est crucial de revoir les procédures de suivi de l'utilisation de la rééducation par les patients et de chercher pourquoi ils n'accèdent pas à ces services, qui sont vitaux en termes de guérison et de restauration de leurs fonctions.

  12. Production of a monoclonal antibody to a membrane antigen of human T-cell leukaemia virus (HTLV1/ATLV)-infected cell lines from a systemic lupus erythematosus (SLE) patient: serological analyses for HTLV1 infections in SLE patients.

    PubMed Central

    Kurata, A; Katamine, S; Fukuda, T; Mine, M; Ikari, N; Kanazawa, H; Matsunaga, M; Eguchi, K; Nagataki, S

    1985-01-01

    Human T-cell leukaemia virus (HTLV1/ATLV), which causes adult T cell leukaemia (ATL), is an infectious, lymphotrophic retrovirus unique for humans. The present study was undertaken to determine whether HTLV1 had any pathogenetic role for systemic lupus erythematosus (SLE). The incidence of antibodies to ATL cell-associated antigens (ATLA) in sera from patients with SLE and other collagen diseases was investigated by an indirect immunofluorescent cytoplasmic staining of an HTLV1-infected cell line (MT-1). A radioimmunoassay was also performed to detect antibodies to HTLV1 protein and crude membrane fraction derived from an HTLV1-producing cell line MT-2. Furthermore, an Epstein-Barr virus (EBV)-transformed B cell line (ES-1) was constructed from an SLE patient, which produced a monoclonal antibody (IgG, lambda) reactive to an HTLV1-related cell-membrane antigen expressed on MT-1 and MT-2 cells. The specific reactivity of the monoclonal antibody was analysed by an indirect immunofluorescent cell-membrane staining and a microcytotoxicity test. The incidence of anti-ATLA antibodies was not different among SLE and other collagen diseases. The monoclonal antibody produced by ES-1 stained and killed HTLV1-infected cell lines specifically, but did not react with other human lymphoid cell lines. This monoclonal antibody failed to react with peripheral blood mononuclear cells (PBMC), mitogen-induced T cell blasts, and iododeoxyuridine-treated T cells from SLE patients. Thus, a possible role of HTLV1 in the aetiology of SLE was not established. PMID:2998659

  13. New subtypes and genetic recombination in HIV type 1-infecting patients with highly active antiretroviral therapy in Peru (2008-2010).

    PubMed

    Yabar, Carlos Augusto; Acuña, Maribel; Gazzo, Cecilia; Salinas, Gabriela; Cárdenas, Fanny; Valverde, Ada; Romero, Soledad

    2012-12-01

    HIV-1 subtype B is the most frequent strain in Peru. However, there is no available data about the genetic diversity of HIV-infected patients receiving highly active antiretroviral therapy (HAART) here. A group of 267 patients in the Peruvian National Treatment Program with virologic failure were tested for genotypic evidence of HIV drug resistance at the Instituto Nacional de Salud (INS) of Peru between March 2008 and December 2010. Viral RNA was extracted from plasma and the segments of the protease (PR) and reverse transcriptase (RT) genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), purified, and fully sequenced. Consensus sequences were submitted to the HIVdb Genotypic Resistance Interpretation Algorithm Database from Stanford University, and then aligned using Clustal X v.2.0 to generate a phylogenetic tree using the maximum likelihood method. Intrasubtype and intersubtype recombination analyses were performed using the SCUEAL program (Subtype Classification by Evolutionary ALgo-rithms). A total of 245 samples (91%) were successfully genotyped. The analysis obtained from the HIVdb program showed 81.5% resistance cases (n=198). The phylogenetic analysis revealed that subtype B was predominant in the population (98.8%), except for new cases of A, C, and H subtypes (n=4). Of these cases, only subtype C was imported. Likewise, recombination analysis revealed nine intersubtype and 20 intrasubtype recombinant cases. This is the first report of the presence of HIV-1 subtypes C and H in Peru. The introduction of new subtypes and circulating recombinants forms can make it difficult to distinguish resistance profiles in patients and consequently affect future treatment strategies against HIV in this country.

  14. New Subtypes and Genetic Recombination in HIV Type 1-Infecting Patients with Highly Active Antiretroviral Therapy in Peru (2008–2010)

    PubMed Central

    Acuña, Maribel; Gazzo, Cecilia; Salinas, Gabriela; Cárdenas, Fanny; Valverde, Ada; Romero, Soledad

    2012-01-01

    Abstract HIV-1 subtype B is the most frequent strain in Peru. However, there is no available data about the genetic diversity of HIV-infected patients receiving highly active antiretroviral therapy (HAART) here. A group of 267 patients in the Peruvian National Treatment Program with virologic failure were tested for genotypic evidence of HIV drug resistance at the Instituto Nacional de Salud (INS) of Peru between March 2008 and December 2010. Viral RNA was extracted from plasma and the segments of the protease (PR) and reverse transcriptase (RT) genes were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), purified, and fully sequenced. Consensus sequences were submitted to the HIVdb Genotypic Resistance Interpretation Algorithm Database from Stanford University, and then aligned using Clustal X v.2.0 to generate a phylogenetic tree using the maximum likelihood method. Intrasubtype and intersubtype recombination analyses were performed using the SCUEAL program (Subtype Classification by Evolutionary ALgo-rithms). A total of 245 samples (91%) were successfully genotyped. The analysis obtained from the HIVdb program showed 81.5% resistance cases (n=198). The phylogenetic analysis revealed that subtype B was predominant in the population (98.8%), except for new cases of A, C, and H subtypes (n=4). Of these cases, only subtype C was imported. Likewise, recombination analysis revealed nine intersubtype and 20 intrasubtype recombinant cases. This is the first report of the presence of HIV-1 subtypes C and H in Peru. The introduction of new subtypes and circulating recombinants forms can make it difficult to distinguish resistance profiles in patients and consequently affect future treatment strategies against HIV in this country. PMID:22559065

  15. Quality of Life in Patients with NSCLC Receiving Maintenance Therapy

    PubMed Central

    Rittmeyer, Achim

    2015-01-01

    Introduction: In the past few years many trials have evaluated the use of maintenance therapy in the treatment of NSCLC stage IV. Both switch as well as continuation maintenance show an improved PFS and overall survival. HRQoL data was only partially published. The aim of this article is to review the published effects of maintenance therapy on HRQoL. Methods: Two PubMed searches were performed using the terms: “maintenance therapy and NSCLC” and “maintenance therapy and NSCLC and HRQoL”. The published data was compared, analysed and evaluated. Results: 272 articles were found dealing with maintenance therapy, and of these 85 articles were found regarding maintenance therapy and HRQoL in NSCLC. Maintenance therapy showed no negative impact on HRQoL but failed to show a real benefit. Some symptoms showed positive trends during maintenance therapy. HRQoL can be used to select patients for maintenance therapy. Conclusions: Maintenance therapy is very safe, improves PFS and OS without impairing HRQoL. Although a positive impact on general QoL could not be demonstrated this is possibly due to the mode of evaluating HRQoL. Patient reported outcomes should be simplified and examined for a longer period of time. PMID:26035509

  16. Prevention and treatment of oral mucositis in patients receiving chemotherapy

    PubMed Central

    Sarrión-Pérez, Maria G.

    2014-01-01

    Oral mucositis is one of the most common side effects of cancer treatment (chemotherapy and/or radiotherapy). It is an inflammatory process that affects the mucosa of the oral cavity, giving rise to erythematous areas in combination with ulcers that can reach a large size. The true importance of oral mucositis is the complications it causes – fundamentally intense pain associated to the oral ulcers, and the risk of overinfection. This in turn may require reduction or even suspension of the antineoplastic treatment, with the risk of seriously worsening the patient prognosis. This points to the importance of establishing therapeutic tools of use in the prevention and/or treatment of mucositis. The present study offers a literature review of all the articles published over the last 10 years referred to the prevention and/or treatment of oral mucositis associated to chemotherapy. Key words:Oral mucositis, management, prevention, treatment, chemotherapy. PMID:24596640

  17. Enhanced CD4+ cellular apoptosis by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with progressive HIV-1 infection

    SciTech Connect

    Wade, Jessica; Sterjovski, Jasminka; Gray, Lachlan; Roche, Michael; Chiavaroli, Lisa; Ellett, Anne; Jakobsen, Martin R.; Cowley, Daniel; Fonseca Pereira, Candida da; Saksena, Nitin; Wang, Bin; Purcell, Damian F.J.; Karlsson, Ingrid; Fenyoe, Eva-Maria; Churchill, Melissa; Gorry, Paul R.

    2010-01-20

    CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1) strains cause CD4+ T-cell loss in most infected individuals, but mechanisms underlying cytopathicity of R5 viruses are poorly understood. We investigated mechanisms contributing to R5 envelope glycoprotein (Env)-mediated cellular apoptosis by constructing a panel of retroviral vectors engineered to co-express GFP and R5 Envs derived from two HIV-1-infected subjects spanning asymptomatic (Early, E-R5 Envs) to late stages of infection (Late, L-R5 Envs). The L-R5 Envs induced significantly more cellular apoptosis than E-R5 Envs, but only in Env-expressing (GFP-positive) cells, and only in cells where CD4 and CCR5 levels were limiting. Studies with fusion-defective Env mutants showed induction of apoptosis required membrane-fusing events. Our results provide evidence for an intracellular mechanism of R5 Env-induced apoptosis of CD4+ cells that requires membrane fusion. Furthermore, they contribute to a better understanding of mechanisms involved in CD4+ T-cell loss in subjects experiencing progressive R5 HIV-1 infection.

  18. Management of specific symptom complexes in patients receiving palliative care

    PubMed Central

    Bruera, E; Neumann, C M

    1998-01-01

    During the past 10 years there have been major changes in the management of the most common symptoms of terminal cancer. Opioid agonists remain the mainstay in the management of cancer pain. Slow-release preparations are currently available for several of these agents. The increased use of opioids has led to the recognition of opioid-induced neurotoxic effects and to the development of effective adjuvant drugs and other strategies to counteract these side effects. A number of drugs are available for the management of symptoms of cachexia, including corticosteroids and progestational drugs. Prokinetic drugs, either alone or in combination with other agents such as corticosteroids, are highly effective in the treatment of chronic nausea. For patients with asthenia, it should first be determined whether there are any reversible causes; if not, corticosteroids and psychostimulants may diminish the symptoms. Haloperidol, other neuroleptics and benzodiazepines may be required to manage hyperactive delirium. Oxygen and opioids are effective in treating dyspnea, whereas there is limited evidence that benzodiazepines provide any relief of this symptom. More research on the assessment and management of these devastating clinical symptoms of cancer is badly needed. PMID:9676549

  19. Myocardial Infarction Risk Among Fracture Patients Receiving Bisphosphonates

    PubMed Central

    Pittman, Cory B.; Davis, Lisa A.; Zeringue, Angelique L.; Caplan, Liron; Wehmeier, Kent R.; Scherrer, Jeffrey F.; Xian, Hong; Cunningham, Francesca E.; McDonald, Jay R.; Arnold, Alexis; Eisen, Seth A.

    2014-01-01

    Objective To determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI). Patients and Methods A cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs (VA), and were derived from encounters at VA facilities between October 1, 1998, and September 30, 2006. The time-to-first AMI was assessed in relation to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database (PBM). Time-to-event analysis was performed using multivariable Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed. Results After controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (HR 1.38; 95% CI, 1.08–1.77; P=0.012). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation. Conclusion These observations conflict with our hypothesis that bisphosphonates have anti-atherogenic effects, and may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required. PMID:24388021

  20. Peptic ulcer disease and other complications in patients receiving dexamethasone palliation for brain metastasis

    SciTech Connect

    Penzner, R.D.; Lipsett, J.A.

    1982-11-01

    A retrospective analysis was done of 106 patients who received radiation therapy for brain metastasis. Dexamethasone therapy was instituted in 97 patients. Peptic ulcer disease developed in 5 of 89 patients (5.6 percent) who received a dosage of at least 12 mg a day, but did not occur in patients who received a lower dose or in those who did not receive steroids. The interval between institution of dexamethasone therapy and the development of peptic ulcer disease ranged from three to nine weeks. Two patients had perforated ulcers, one of whom required surgical resection. Peptic ulcer disease contributed to the general deterioration and death of three of the five patients. Overall, in 14 of the 89 patients (15.7 percent) a complication of steroid therapy developed in the form of peptic ulcer disease, steroid myopathy or diabetes mellitus (or a combination of these).

  1. The patient-provider discordance in patients' needs assessment: a qualitative study in breast cancer patients receiving oral chemotherapy.

    PubMed

    Wei, Chunlan; Nengliang, Yao; Yan, Wang; Qiong, Fang; Yuan, Changrong

    2017-01-01

    To explore the differing perspectives of patients and providers and their assessment of supportive care needs in breast cancer patients receiving oral chemotherapy. The patient-provider concordance in patients' needs assessment is critical to the effective management of cancer. Self-administered oral chemotherapy greatly shifts responsibilities for side-effect monitoring, symptom management and dose adjustments from the provider to the patient. Home-based care plans will be central to the effective management of these patients. A descriptive qualitative design was used. A purposive sample of nine breast cancer patients, four oncologists and four oncology nurses were recruited in Shanghai, China. Semi-structured and in-depth interviews were conducted to collect data. A qualitative content analysis aimed at finding manifest and latent meanings of data was applied to analyse the information. Four themes of needs emerged from the interviews with patients and providers: information/knowledge, communication, social support and symptom management, but patients and providers only agreed on the assessment of symptom and side-effects management needs. Patients want more positive encouraging information from providers, but providers think patients need more information of efficacy and safety. Patients appreciate support from other peer patients with similar experiences, but providers think the support from families and friends are readily available to them. Patients discussed their spiritual needs, while oncologists see the need to improve patient adherence to medication. Breast cancer patients differed from their providers in assessment of healthcare needs. Further investigation of the relationships between patient-provider discordance and patient outcomes may guide interventions to improve care for cancer patients receiving oral chemotherapy. Oncology nurses should develop a holistic home-based care plan by exploring and integrating the discordance of needs assessment of

  2. Neutralising antibodies in patients with multiple myeloma receiving maintenance therapy with interferon alpha 2b.

    PubMed Central

    Bell, J. B.; Barfoot, R.; Iveson, T.; Powles, R. L.; Millar, B. C.

    1994-01-01

    In a study of 29 patients who were receiving or had received interferon alpha 2b (IFN-alpha 2b) as maintenance therapy for multiple myeloma, antibodies were detected in 58% (17/29) of patients measured by a solid-phase enzyme-linked immunosorbent assay (ELISA). Only 7/17 patients who were positive for antibody in the ELISA had neutralising antibody to IFN-alpha 2b, measured by virus growth inhibition. These patients comprised six who were receiving IFN-alpha 2b at the time of assessment and one who had finished treatment. Among patients who were receiving the cytokine, four had progressive disease, one was in complete remission and one in partial remission. Neutralising activity was also detected to natural human leucocyte IFN-alpha in the same patients. Two patients who were positive for neutralising antibody remain in remission and are continuing to receive IFN-alpha 2b. These two patients have since lost their neutralising titre. No neutralising antibody to IFN-alpha 2b or natural human leucocyte IFN-alpha was detected in serum from six normal donors. The data suggest that neutralising antibody formation in patients with multiple myeloma is not responsible for relapse in patients receiving IFN-alpha 2b. The transient nature of neutralising antibody production in patients who remain in remission suggests that this response to IFN-alpha 2b is not associated with memory B cells. PMID:7917911

  3. Predicting postoperative vomiting among orthopedic patients receiving patient-controlled epidural analgesia using SVM and LR.

    PubMed

    Wu, Hsin-Yun; Gong, Cihun-Siyong Alex; Lin, Shih-Pin; Chang, Kuang-Yi; Tsou, Mei-Yung; Ting, Chien-Kun

    2016-06-01

    Patient-controlled epidural analgesia (PCEA) has been applied to reduce postoperative pain in orthopedic surgical patients. Unfortunately, PCEA is occasionally accompanied by nausea and vomiting. The logistic regression (LR) model is widely used to predict vomiting, and recently support vector machines (SVM), a supervised machine learning method, has been used for classification and prediction. Unlike our previous work which compared Artificial Neural Networks (ANNs) with LR, this study uses a SVM-based predictive model to identify patients with high risk of vomiting during PCEA and comparing results with those derived from the LR-based model. From January to March 2007, data from 195 patients undergoing PCEA following orthopedic surgery were applied to develop two predictive models. 75% of the data were randomly selected for training, while the remainder was used for testing to validate predictive performance. The area under curve (AUC) was measured using the Receiver Operating Characteristic curve (ROC). The area under ROC curves of LR and SVM models were 0.734 and 0.929, respectively. A computer-based predictive model can be used to identify those who are at high risk for vomiting after PCEA, allowing for patient-specific therapeutic intervention or the use of alternative analgesic methods.

  4. Immune Reconstitution in Severely Immunosuppressed Antiretroviral-Naive HIV-1-Infected Patients Starting Efavirenz, Lopinavir-Ritonavir, or Atazanavir-Ritonavir Plus Tenofovir/Emtricitabine: Final 48-Week Results (The Advanz-3 Trial).

    PubMed

    Miro, Jose M; Manzardo, Christian; Ferrer, Elena; Loncà, Montserrat; Guardo, Alberto C; Podzamczer, Daniel; Domingo, Pere; Curran, Adrian; Clotet, Bonaventura; Cruceta, Anna; Lozano, Francisco; Pérez, Iñaki; Plana, Montserrat; Gatell, Jose M

    2015-06-01

    Few randomized clinical trials have investigated antiretroviral regimens in very advanced HIV-1-infected patients. The objective was to study the immune reconstitution in very immunosuppressed antiretroviral-naive, HIV-1-infected individuals by comparing an efavirenz-based regimen with 2 ritonavir-boosted protease inhibitor regimens. Randomized, controlled, open-label, multicenter clinical trial. Eighty-nine HIV-1-infected antiretroviral-naive patients with <100 CD4 cells per cubic millimeter were randomly assigned in a 1:1:1 ratio to efavirenz (n = 29), atazanavir/ritonavir (n = 30), or lopinavir/ritonavir (n = 30) combined with tenofovir plus emtricitabine. The primary outcome was median increase in CD4 cell count at week 48. Secondary end points were the proportion of patients with HIV-1 RNA <50 copies per milliliter, adverse events, disease progression, and death. In the on-treatment analysis, the median (interquartile range) increase in the CD4 count after 48 weeks was +193 (129-349) cells per microliter in the efavirenz arm, +197 (146-238) cells per microliter in the ritonavir-boosted atazanavir arm, and +205 (178-327) cells per microliter in the ritonavir-boosted lopinavir arm (P = 0.73). The percentage of patients achieving viral suppression was similar in all 3 treatment arms at 48 weeks {efavirenz, 85.71% [95% confidence interval (CI): 68.5 to 94.3]; atazanavir, 80% [95% CI: 62.7 to 90.5]; and lopinavir, 82.8% [95% CI: 65.5 to 92.4]; P = 0.88}. Bacterial translocation, inflammation, immune activation, and apoptotic markers, but not D-dimer, declined significantly and similarly in the 3 treatment arms. Adverse events had a similar incidence in all 3 antiretroviral regimens. No patients died. The immune reconstitution induced by an efavirenz-based regimen in very advanced HIV-1-infected patients was similar to that induced by a ritonavir-boosted protease inhibitor-based regimen (ClinicalTrials.gov registration number: NCT00532168).

  5. Kitten-transmitted Bordetella bronchiseptica infection in a patient receiving temozolomide for glioblastoma.

    PubMed

    Redelman-Sidi, Gil; Grommes, Christian; Papanicolaou, Genovefa

    2011-04-01

    Bordetella bronchiseptica is a gram negative coccobacillus that can be transmitted from domestic animals and cause severe infections in immunocompromised patients. A 56-year-old man with a left parietal glioblastoma was treated with resection, radiation and concomitant and adjuvant temozolomide chemotherapy. He received bevacizumab for progression, and dose dense metronomic temozolomide was added for additional progression. He developed chronic cough and was diagnosed with B. bronchiseptica infection. This is the first reported case of B. bronchiseptica infection in a patient receiving temozolomide. The infection was likely acquired from an infected kitten. Patients receiving temozolomide should be counseled on the risks of acquiring zoonotic infections, including B. bronchiseptica, from their pets.

  6. Information needs of cancer patients receiving chemotherapy in an ambulatory-care setting.

    PubMed

    Lock, Karen K; Willson, Barbara

    2002-12-01

    The purpose of this study was to assess the information needs of cancer patients receiving chemotherapy and to explore their preferred styles of receiving education in an ambulatory-care setting. Patient information needs and preferences were measured using a 17-item questionnaire. This descriptive study included a sample of 101 cancer patients undergoing outpatient chemotherapy. The most commonly expressed information needs concerned: side effects of treatment, drug information, and coping strategies. Some patients expressed a preference for information in their primary language. The results support the use of online learning in this setting. Patients identified one-on-one discussion with nurses and doctors as the preferred way to receive information. In order to meet the individual needs of cancer patients, education should be provided in a variety of learning modalities. The results of this study should help to guide patient education initiatives in oncology ambulatory care.

  7. Assessing Selenium, Manganese, and Iodine Status in Pediatric Patients Receiving Parenteral Nutrition.

    PubMed

    Johnsen, Jacob Clarke; Reese, Susan Anne; Mackay, Mark; Anderson, Collin R; Jackson, Daniel; Paul, Irasema Libertad

    2017-08-01

    Pediatric patients who are receiving parenteral nutrition (PN) unsupplemented with trace minerals can become deficient. Due to shortages in trace mineral products and the 2004 American Society for Parenteral and Enteral Nutrition report stating that individualized trace element supplementation may be warranted, a review was conducted concerning the trace minerals selenium (Se), manganese (Mn), and iodine (I). A retrospective review of pediatric patients receiving PN that contained Se and Mn was conducted to determine if a difference existed between them and patients receiving PN without Se and Mn. Statistical analysis was done to assess a difference between trace mineral levels and the time to deficiency between supplemented and unsupplemented patients. Unsupplemented I patients had urine I levels assessed to determine deficiencies in patients receiving PN. Plasma Se levels were measured at a mean of 20 days for supplemented patients (n = 131) and 19 days for nonsupplemented patients (n = 57) with no difference between groups ( P = .2973). Plasma Mn levels were measured at a mean of 28 days, showing no statistical difference ( P = .721). Of the 177 nonsupplemented I patients, 74% demonstrated I deficiencies without supplementation. Time to the development of a Se, Mn, or I deficiency is important to guide supplementation of exclusive PN in children when trace mineral products are short in supply. Our retrospective experience supports assessment of the trace minerals Se at 21 days and Mn at 30 days. It also suggests that some pediatric patients receiving PN are deficient in I.

  8. Homocysteine, folate, vitamin B-12 and vitamin B-6 in patients receiving antiepileptic drug monotherapy.

    PubMed

    Tamura, T; Aiso, K; Johnston, K E; Black, L; Faught, E

    2000-06-01

    We hypothesized that elevated plasma homocysteine concentrations (hyperhomocysteinemia) exist in patients receiving antiepileptic drugs (AED), and a long-term administration of AED may result in an increased risk of occlusive vascular disease in these patients. A total of 62 patients who received AED monotherapy (phenytoin, lamotrigine, carbamazepine or valproate) participated in this study. Blood concentrations of homocysteine, folate, vitamin B-12 and pyridoxal-5'-phosphate (PLP, a coenzyme form of vitamin B-6) were measured, and thermolabile genotypes of 5, 10-methylenetetrahydrofolate reductase (MTHFR) were also determined. Of 62 patients, only seven (11.4%) had hyperhomocysteinemia. Of 20 patients who received phenytoin, three (15.0%) had hyperhomocysteinemia, whereas 85% of these had plasma folate concentrations below the normal range. However, erythrocyte folate concentrations were abnormally low in only 25% of the patients who received phenytoin. Valproate administration increased serum vitamin B-12 concentrations. Over 55% of the entire patients had PLP concentrations below the normal range, although the reason is unknown. Only three patients had the homozygous thermolabile genotype of MTHFR; therefore, meaningful statistical analysis was not possible in this study. However, one patient with homozygous genotype who received phenytoin therapy had hyperhomocysteinemia with poor folate nutritional status, and the other two had normal homocysteine concentrations with normal folate status. Our data suggest that hyperhomocysteinemia is not a serious clinical concern in epileptic patients when folate nutriture is adequate.

  9. Risk of epilepsy in stroke patients receiving acupuncture treatment: a nationwide retrospective matched-cohort study

    PubMed Central

    Weng, Shu-Wen; Liao, Chien-Chang; Yeh, Chun-Chieh; Chen, Ta-Liang; Lane, Hsin-Long; Lin, Jaung-Geng; Shih, Chun-Chuan

    2016-01-01

    Objective To investigate the risk of epilepsy in stroke patients receiving and not receiving acupuncture treatment. Design Retrospective cohort study. Setting This study was based on Taiwan's National Health Insurance Research Database that included information on stroke patients hospitalised between 1 January 2000 and 31 December 2004. Participants We identified 42 040 patients hospitalised with newly diagnosed stroke who were aged 20 years and above. Primary and secondary outcome measures We compared incident epilepsy during the follow-up period until the end of 2009 in stroke patients who were and were not receiving acupuncture. The adjusted HRs and 95% CIs of epilepsy associated with acupuncture were calculated using multivariate Cox proportional hazard regression. Results Stroke patients who received acupuncture treatment (9.8 per 1000 person-years) experienced a reduced incidence of epilepsy compared to those who did not receive acupuncture treatment (11.5 per 1000 person-years), with an HR of 0.74 (95% CI 0.68 to 0.80) after adjustment for sociodemographic factors and coexisting medical conditions. Acupuncture treatment was associated with a decreased risk of epilepsy, particularly among stroke patients aged 20–69 years. The log-rank test probability curve indicated that stroke patients receiving acupuncture treatment had a reduced probability of epilepsy compared with individuals who did not receive acupuncture treatment during the follow-up period (p<0.0001). Conclusions Stroke patients who received acupuncture treatment had a reduced risk of epilepsy compared with those not receiving acupuncture treatment. However, the protective effects associated with acupuncture treatment require further validation in prospective cohort studies. PMID:27412100

  10. A simplification trial switching from nucleoside reverse transcriptase inhibitors to once-daily fixed-dose abacavir/lamivudine or tenofovir/emtricitabine in HIV-1-infected patients with virological suppression.

    PubMed

    Martínez, Esteban; Arranz, José A; Podzamczer, Daniel; Loncá, Montserrat; Sanz, José; Barragán, Patricia; Ribera, Esteban; Knobel, Hernando; Roca, Victor; Gutiérrez, Félix; Blanco, José L; Mallolas, Josep; Llibre, Josep M; Clotet, Bonaventura; Dalmau, David; Segura, Ferran; Arribas, José R; Cosín, Jaime; Barrufet, Pilar; Casas, Esperanza; Ferrer, Elena; Curran, Adrià; González, Alicia; Pich, Judit; Cruceta, Ana; Arnaiz, Joan A; Miró, José M; Gatell, José M

    2009-07-01

    Data comparing abacavir/lamivudine versus tenofovir/emtricitabine in antiretroviral-naive patients are controversial. We compared 48-week efficacy and safety of these combinations as substitutes of nucleosides in patients with virological suppression. We randomly assigned 333 HIV-1-infected patients on lamivudine-containing triple regimens with <200 copies per milliliter for at least 6 months to switch their nucleosides to either abacavir/lamivudine (n = 167) or tenofovir/emtricitabine (n = 166). The primary outcome was treatment failure ["switching = failure" intention to treat (ITT) analysis, noninferiority margin 12.5%]. Secondary outcomes were time to treatment failure, virological failure, adverse events, and changes in CD4 count, fasting plasma lipids, lipodystrophy, body fat, bone mineral density, and renal function. Treatment failure occurred in 32 patients (19%) on abacavir/lamivudine and 22 patients (13%) on tenofovir/emtricitabine [difference 5.9%; (95% confidence interval -2.1% to 14.0%), P = 0.06]. Four patients in the abacavir/lamivudine group versus none in the tenofovir/emtricitabine group developed virological failure [difference 2.4; (95% confidence interval 0.05 to 6.0), P = 0.04]. Twenty-three patients (14%) assigned to abacavir/lamivudine and 10 (6%) to tenofovir/lamivudine experienced grade 3 or 4 adverse effects (P = 0.03). CD4 counts and plasma lipids showed higher increments in the abacavir/lamivudine group than in the tenofovir/emtricitabine group. In HIV-1-infected patients with virological suppression, abacavir/lamivudine did not meet the noninferiority outcome for treatment efficacy compared with tenofovir/emtricitabine.

  11. Evaluating the Effect of Zingiber Officinalis on Nausea and Vomiting in Patients Receiving Cisplatin Based Regimens

    PubMed Central

    Fahimi, Fanak; Khodadad, Kian; Amini, Somayeh; Naghibi, Farzaneh; Salamzadeh, Jamshid; Baniasadi, Shadi

    2011-01-01

    Ginger, the rhizome of Zingiber officinalis, has long been used as herbal medicine for its antiemetic effect. For evaluating the effect of zingiber officinalis on nausea and vomiting (N and V) in patients receiving cisplatin based regimens, a randomized double-blind placebo-controlled cross-over clinical trial was carried out in patients receiving cisplatin in combination with other chemotherapeutic agents. The patients were randomly assigned to receive ginger capsules (rhizome of zingiber officinalis) or placebo in their first cycle of the study. All patients received standard antiemetics for chemotherapy induced nausea and vomiting (CINV). The patients were crossed-over to receive ginger or placebo in their next cycle of chemotherapy. Among 36 eligible patients who received both cycles of treatment, there were no difference in prevalence, severity, and duration of both acute and delayed N and V. Addition of ginger to the standard antiemetic regimen has shown no advantage in reducing acute and delayed N and V in patients with cisplatin-based regimen in this study. PMID:24250368

  12. Heterogeneity of patients receiving artificial nutrition in Japanese psychiatric hospitals: a cross-sectional study.

    PubMed

    Hirao, Akihiko; Abe, Keiichi; Takayama, Keiko; Kondo, Keiko; Yokota, Osamu; Sato, Yoshiki; Norikiyo, Taizo; Sato, Soichiro; Nakashima, Tadao; Hayashi, Hideki; Nakata, Kenji; Asaba, Hiroyuki; Tanaka, Kazuyoshi; Tanaka, Ritsuho; Morisada, Yumi; Itakura, Hisakazu; Honda, Hajime; Okabe, Nobuyuki; Oshima, Etsuko; Terada, Seishi

    2016-11-01

    Artificial nutrition, including tube feeding, continues to be given to dementia patients in numerous geriatric facilities in Japan. However, the clinical characteristics of patients receiving artificial nutrition have not been fully investigated. Therefore, we tried to evaluate the clinical features of those patients in this study. Various clinical characteristics of all inpatients at 18 of 20 psychiatric hospitals in Okayama Prefecture, Japan, with a percutaneous endoscopic gastrostomy tube, nasogastric tube, or total parenteral nutrition were evaluated. Two hundred twenty-one patients (5.4% of all inpatients) had been receiving artificial nutrition for more than 1 month, and 187 (130 women, 57 men; 84.6% of 221 patients) were fully investigated. The mean age was 78.3 years old, and the mean duration of artificial nutrition was 29.8 months. Eighty-four patients (44.7% of 187 patients) were receiving artificial nutrition for more than 2 years. Patients with Alzheimer's disease (n = 78) formed the biggest group, schizophrenia (n = 37) the second, and vascular dementia (n = 26) the third. About one-fifth of the subjects receiving artificial nutrition were in a vegetative state. More than a few patients with mental disorders, including schizophrenia, also received long-term artificial nutrition. We should pay more attention to chronic dysphasia syndrome in mental disorders. © 2016 The Authors. Psychogeriatrics © 2016 Japanese Psychogeriatric Society.

  13. Five-Year Survival Among Stage IIIA Lung Cancer Patients Receiving Two Different Treatment Modalities.

    PubMed

    Bilfinger, Thomas; Keresztes, Roger; Albano, Denise; Nemesure, Barbara

    2016-07-21

    BACKGROUND Five-year survival rates among stage IIIA lung cancer patients range between 2% and 15%, and there is currently no consensus regarding optimal treatment approaches for these patients. The current investigation evaluated survival outcomes among stage IIIA lung cancer patients receiving 2 different treatment modalities, neoadjuvant chemotherapy followed by resection versus chemoradiation alone. MATERIAL AND METHODS This retrospective study is based on 127 patients attending the Lung Cancer Evaluation Center at Stony Brook Cancer Center between 2002 and 2014. Patients were treated either with neoadjuvant chemotherapy followed by resection or a regimen of chemoradiation alone. Kaplan-Meier curves were used to compare survival outcomes between groups and Cox proportional hazard models were used to evaluate treatment effects on survival, while adjusting for possible confounders. RESULTS Approximately one-fourth (n=33) of patients received neoadjuvant chemotherapy followed by surgery, whereas 94 patients received definitive chemoradiation. Patients in the surgical group were found to be significantly younger than those receiving chemoradiation alone (60.1 vs. 67.9 years, respectively; p=0.001). Five-year survival among patients receiving preoperative chemotherapy followed by resection was significantly higher than that among patients receiving chemoradiation alone (63% vs. 19%, respectively; p<0.001), whereas the hazard ratio (HR) was 3-4 times greater in the latter group (HR=3.77, 95% confidence interval=1.87, 7.61). CONCLUSIONS Findings from this study indicate that preoperative chemotherapy followed by resection can improve survival outcomes for stage IIIA lung cancer patients compared with chemoradiation alone. The results reflect a select surgical group of patients; thus, the data highlight the need to develop new therapies that may result in more patients being viable surgical candidates.

  14. Patient-Reported Outcome Instruments for Physical Symptoms Among Patients Receiving Maintenance Dialysis: A Systematic Review

    PubMed Central

    Flythe, Jennifer E.; Powell, Jill D.; Poulton, Caroline J.; Westreich, Katherine D.; Handler, Lara; Reeve, Bryce B.; Carey, Timothy S.

    2015-01-01

    Background Patients with end-stage renal disease (ESRD) receiving dialysis have poor health-related quality of life (HRQoL). Physical symptoms are highly prevalent among dialysis-dependent patients and play important roles in HRQoL. A range of symptom assessment tools have been used in dialysis-dependent patients, but there has been no previous systematic assessment of the existing symptom measures’ content, validity, and reliability. Study Design systematic review of the literature Settings & Population ESRD patients on maintenance dialysis Selection Criteria for Studies instruments with ≥3 physical symptoms previously used in dialysis-dependent patients and evidence of validity or reliability testing Intervention patient-reported physical symptom assessment instrument Outcomes instrument symptom-related content, validity, and reliability Results From 3,148 screened abstracts, 89 full-text articles were eligible for review. After article exclusion and further article identification via reference reviews, 58 articles on 23 symptom assessment instruments with documented reliability or validity testing were identified. Of the assessment instruments, 43.5% were generic and 56.5% were ESRD-specific. Symptoms most frequently assessed were fatigue, shortness of breath, insomnia, nausea and vomiting, and appetite. The instruments varied widely in respondent time burden, recall period, and symptom attributes. Few instruments considered recall periods less than 2 weeks and few assessed a range of symptom attributes. Psychometric testing was completed for congruent validity (70%), known group validity (25%), responsiveness (30%), internal consistency (78%), and test-retest reliability (65%). Content validity was assessed in dialysis populations in 57% of the 23 instruments. Limitations Consideration of physical symptoms only and exclusion of single symptom-focused instruments Conclusions The number of available instruments focused exclusively on physical symptoms in

  15. Patient-Reported Outcome Instruments for Physical Symptoms Among Patients Receiving Maintenance Dialysis: A Systematic Review.

    PubMed

    Flythe, Jennifer E; Powell, Jill D; Poulton, Caroline J; Westreich, Katherine D; Handler, Lara; Reeve, Bryce B; Carey, Timothy S

    2015-12-01

    Patients with end-stage renal disease (ESRD) receiving dialysis have poor health-related quality of life. Physical symptoms are highly prevalent among dialysis-dependent patients and play important roles in health-related quality of life. A range of symptom assessment tools have been used in dialysis-dependent patients, but there has been no previous systematic assessment of the existing symptom measures' content, validity, and reliability. Systematic review of the literature. Patients with ESRD on maintenance dialysis therapy. Instruments with 3 or more physical symptoms previously used in dialysis-dependent patients and evidence of validity or reliability testing. Patient-reported physical symptom assessment instrument. Instrument symptom-related content, validity, and reliability. From 3,148 screened abstracts, 89 full-text articles were eligible for review. After article exclusion and further article identification by reference reviews, 58 articles on 23 symptom assessment instruments with documented reliability or validity testing were identified. Of the assessment instruments, 43.5% were generic and 56.5% were ESRD specific. Symptoms most frequently assessed were fatigue, shortness of breath, insomnia, nausea and vomiting, and appetite. Instruments varied widely in respondent time burden, recall period, and symptom attributes. Few instruments considered recall periods less than 2 weeks and few assessed a range of symptom attributes. Psychometric testing was completed for congruent validity (70%), known-group validity (25%), responsiveness (30%), internal consistency (78%), and test-retest reliability (65%). Content validity was assessed in dialysis populations in 57% of the 23 instruments. Consideration of physical symptoms only and exclusion of single symptom-focused instruments. The number of available instruments focused exclusively on physical symptoms in dialysis patients is limited. Few symptom-containing instruments have short recall periods, assess

  16. Efficacy of etravirine combined with darunavir or other ritonavir-boosted protease inhibitors in HIV-1-infected patients: an observational study using pooled European cohort data.

    PubMed

    Vingerhoets, J; Calvez, V; Flandre, P; Marcelin, A-G; Ceccherini-Silberstein, F; Perno, C-F; Mercedes Santoro, M; Bateson, R; Nelson, M; Cozzi-Lepri, A; Grarup, J; Lundgren, J; Incardona, F; Kaiser, R; Sonnerborg, A; Clotet, B; Paredes, R; Günthard, H F; Ledergerber, B; Hoogstoel, A; Nijs, S; Tambuyzer, L; Lavreys, L; Opsomer, M

    2015-05-01

    This observational study in antiretroviral treatment-experienced, HIV-1-infected adults explored the efficacy of etravirine plus darunavir/ritonavir (DRV group; n = 999) vs. etravirine plus an alternative boosted protease inhibitor (other PI group; n = 116) using pooled European cohort data. Two international (EuroSIDA; EUResist Network) and five national (France, Italy, Spain, Switzerland and UK) cohorts provided data (collected in 2007-2012). Stratum-adjusted (for confounding factors) Mantel-Haenszel differences in virological responses (viral load < 50 HIV-1 RNA copies/mL) and odds ratios (ORs) with 95% confidence intervals (CIs) were derived. Baseline characteristics were balanced between groups except for previous use of antiretrovirals (≥ 10: 63% in the DRV group vs. 49% in the other PI group), including previous use of at least three PIs (64% vs. 53%, respectively) and mean number of PI resistance mutations (2.3 vs. 1.9, respectively). Week 24 responses were 73% vs. 75% (observed) and 49% vs. 43% (missing = failure), respectively. Week 48 responses were 75% vs. 73% and 32% vs. 30%, respectively. All 95% CIs around unadjusted and adjusted differences encompassed 0 (difference in responses) or 1 (ORs). While ORs by cohort indicated heterogeneity in response, for pooled data the difference between unadjusted and adjusted for cohort ORs was small. These data do not indicate a difference in response between the DRV and other PI groups, although caution should be applied given the small size of the other PI group and the lack of randomization. This suggests that the efficacy and virology results from DUET can be extrapolated to a regimen of etravirine with a boosted PI other than darunavir/ritonavir. © 2015 British HIV Association.

  17. Assessment of the appropriateness of naloxone administration to patients receiving long-term opioid therapy.

    PubMed

    Facey, Caroline; Brooks, David; Boland, Jason W

    2016-01-01

    The most dangerous adverse effect of opioids is respiratory depression. Naloxone is used to reverse this, although in patients receiving long-term opioid therapy it can cause acute opioid withdrawal and opioid-refractory pain. To determine if naloxone is appropriately administered to patients receiving long-term opioid therapy. This retrospective case series based on chart reviews systematically identified patients over one year in a district general hospital. All patients aged 18 years or older receiving long-term opioid therapy admitted to medicine, surgery or the high dependency unit who were administered naloxone during their admission were included. A total of 1206 patient drug administration records were reviewed. Sixteen patients receiving long-term opioid therapy were administered naloxone. Twelve of these did not have opioid-induced respiratory depression and four did not have respiratory rate and oxygen saturations documented in the medical notes. All naloxone doses administered were higher than those recommended by national guidelines for this patient group. No patient receiving long-term opioid therapy who was administered naloxone had evidence of respiratory depression. More thorough assessment and documentation are needed. Verbal and physical stimulation as well as oxygenation should be considered prior to naloxone administration; this should be followed by close observation, hydration, renal function tests and opioid dose review.

  18. Predictive Factors for Radiation Pneumonitis in Hodgkin Lymphoma Patients Receiving Combined-Modality Therapy

    SciTech Connect

    Fox, Amy M.; Dosoretz, Arie P.; Mauch, Peter M.; Chen, Yu-Hui; Fisher, David C.; LaCasce, Ann S.; Freedman, Arnold S.; Silver, Barbara; Ng, Andrea K.

    2012-05-01

    Purpose: This study sought to quantify the risk of radiation pneumonitis (RP) in Hodgkin lymphoma (HL) patients receiving mediastinal radiation therapy (RT) and to identify predictive factors for RP. Methods and Materials: We identified 75 patients with newly diagnosed HL treated with mediastinal RT and 17 patients with relapsed/refractory HL treated with mediastinal RT before or after transplant. Lung dose-volumetric parameters including mean lung dose and percentage of lungs receiving 20 Gy were calculated. Factors associated with RP were explored by use of the Fisher exact test. Results: RP developed in 7 patients (10%) who received mediastinal RT as part of initial therapy (Radiation Therapy Oncology Group Grade 1 in 6 cases). A mean lung dose of 13.5 Gy or greater (p = 0.04) and percentage of lungs receiving 20 Gy of 33.5% or greater (p = 0.009) significantly predicted for RP. RP developed in 6 patients (35%) with relapsed/refractory HL treated with peri-transplant mediastinal RT (Grade 3 in 4 cases). Pre-transplant mediastinal RT, compared with post-transplant mediastinal RT, significantly predicted for Grade 3 RP (57% vs. 0%, p = 0.015). Conclusions: We identified threshold lung metrics predicting for RP in HL patients receiving mediastinal RT as part of initial therapy, with the majority of cases being of mild severity. The risk of RP is significantly higher with peri-transplant mediastinal RT, especially among those who receive pre-transplant RT.

  19. Comparing the clinical outcomes in patients with atrial fibrillation receiving dual antiplatelet therapy and patients receiving an addition of an anticoagulant after coronary stent implantation

    PubMed Central

    Chaudhary, Nabin; Bundhun, Pravesh Kumar; Yan, He

    2016-01-01

    Abstract Background: Data regarding the clinical outcomes in patients with atrial fibrillation (AF) receiving dual antiplatelet therapy (DAPT) and an anticoagulant in addition to DAPT (DAPT + vitamin K antagonist [VKA]) after coronary stent implantation are still controversial. Therefore, in order to solve this issue, we aim to compare the adverse clinical outcomes in AF patients receiving DAPT and DAPT + VKA after percutaneous coronary intervention and stenting (PCI-S). Methods: Observational studies comparing the adverse clinical outcomes such as major bleeding, major adverse cardiovascular events, stroke, myocardial infarction, all-cause mortality, and stent thrombosis (ST) in AF patients receiving DAPT + VKA therapy, and DAPT after PCI-S have been searched from Medline, EMBASE, and PubMed databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to express the pooled effect on discontinuous variables, and the pooled analyses were performed with RevMan 5.3. Results: Eighteen studies consisting of a total of 20,456 patients with AF (7203 patients received DAPT + VKA and 13,253 patients received DAPT after PCI-S) were included in this meta-analysis. At a mean follow-up period of 15 months, the risk of major bleeding was significantly higher in DAPT + VKA group, with OR 0.62 (95% CI 0.50–0.77, P < 0.0001). There was no significant differences in myocardial infarction and major adverse cardiovascular event between DAPT + VKA and DAPT, with OR 1.27 (95% CI 0.92–1.77, P = 0.15) and OR 1.17 (95% CI 0.99–1.39, P = 0.07), respectively. However, the ST, stroke, and all-cause mortality were significantly lower in the DAPT + VKA group, with OR 1.98 (95% CI 1.03–3.81, P = 0.04), 1.59 (95% CI 1.08–2.34, P = 0.02), and 1.41 (95% CI 1.03–1.94, P = 0.03), respectively. Conclusion: At a mean follow-up period of 15 months, DAPT + VKA was associated with significantly lower risk of stroke, ST, and

  20. Phase II Study of Bevacizumab in Patients With HIV-Associated Kaposi's Sarcoma Receiving Antiretroviral Therapy

    PubMed Central

    Uldrick, Thomas S.; Wyvill, Kathleen M.; Kumar, Pallavi; O'Mahony, Deirdre; Bernstein, Wendy; Aleman, Karen; Polizzotto, Mark N.; Steinberg, Seth M.; Pittaluga, Stefania; Marshall, Vickie; Whitby, Denise; Little, Richard F.; Yarchoan, Robert

    2012-01-01

    Purpose Alternatives to cytotoxic agents are desirable for patients with HIV-associated Kaposi's sarcoma (KS). Vascular endothelial growth factor-A (VEGF-A) contributes to KS pathogenesis. We evaluated the humanized anti–VEGF-A monoclonal antibody, bevacizumab, in patients with HIV-KS. Patients and Methods Patients with HIV-KS who either experienced progression while receiving highly active antiretroviral therapy (HAART) for at least 1 month or did not regress despite HAART for at least 4 months were administered bevacizumab 15 mg/kg intravenously on days 1 and 8 and then every 3 weeks. The primary objective was assessment of antitumor activity using modified AIDS Clinical Trial Group (ACTG) criteria for HIV-KS. HIV-uninfected patients were also eligible and observed separately. Results Seventeen HIV-infected patients were enrolled. Fourteen patients had been receiving effective HAART for at least 6 months (median, 1 year). Thirteen patients had advanced disease (ACTG T1), 13 patients had received prior chemotherapy for KS, and seven patients had CD4 count less than 200 cells/μL. Median number of cycles was 10 (range, 1 to 37 cycles); median follow-up was 8.3 months (range, 3 to 36 months). Of 16 assessable patients, best tumor responses observed were complete response (CR) in three patients (19%), partial response (PR) in two patients (12%), stable disease in nine patients (56%), and progressive disease in two patients (12%). Overall response rate (CR + PR) was 31% (95% CI, 11% to 58.7%). Four of five responders had received prior chemotherapy for KS. Over 202 cycles, grade 3 to 4 adverse events at least possibly attributed to therapy included hypertension (n = 7), neutropenia (n = 5), cellulitis (n = 3), and headache (n = 2). Conclusion Bevacizumab is tolerated in patients with HIV-KS and has activity in a subset of patients. PMID:22430271

  1. Safety of electroconvulsive therapy in patients receiving long-term warfarin therapy.

    PubMed

    Mehta, Vinay; Mueller, Paul S; Gonzalez-Arriaza, Heydy L; Pankratz, V Shane; Rummans, Teresa A

    2004-11-01

    To investigate the safety of electroconvulsive therapy (ECT) in patients receiving long-term warfarin therapy. Retrospective data were reviewed for 35 consecutively hospitalized patients who received long-term warfarin therapy and ECT at the Mayo Clinic in Rochester, Minn, between January 1, 1994, and December 31, 2001. A total of 300 ECT treatments were administered to the 35 patients. Of 284 ECT treatments for which data were available, no ECT-related complications due to anticoagulation occurred despite increases in blood pressure and pulse rate. One patient experienced ventricular tachycardia, resulting in transfer to a cardiology service for temporary monitoring. No other serious ECT-related adverse effects were noted. The rate of intertreatment delirium was similar to that reported in other studies. Electroconvulsive therapy in patients receiving long-term warfarin therapy appears to be safe. Although no major adverse effects were identified in our case series, additional prospective evaluation is warranted.

  2. Impact of gender on response to highly active antiretroviral therapy in HIV-1 infected patients: a nationwide population-based cohort study

    PubMed Central

    2012-01-01

    Background Impact of gender on time to initiation, response to and risk of modification of highly active antiretroviral therapy (HAART) in HIV-1 infected individuals is still controversial. Methods From a nationwide cohort of Danish HIV infected individuals we identified all heterosexually infected women (N=587) and heterosexually infected men (N=583) with no record of Hepatitis C infection diagnosed with HIV after 1 January 1997. Among these subjects, 473 women (81%) and 435 men (75%) initiated HAART from 1 January 1997 to 31 December 2009. We used Cox regression to calculate hazard ratio (HR) for time to initiation of HAART, Poisson regression to assess incidence rate ratios (IRR) of risk of treatment modification the first year, logistic regression to estimate differences in the proportion with an undetectable viral load, and linear regression to detect differences in CD4 count at year 1, 3 and 6 after start of HAART. Results At initiation of HAART, women were younger, predominantly of Black ethnicity and had a higher CD4 count (adjusted p=0.026) and lower viral load (adjusted p=0.0003). When repeating the analysis excluding pregnant women no difference was seen in CD4 counts (adjusted p=0.21). We observed no delay in time to initiation of HAART in women compared to men (HR 0.91, 95% CI 0.79-1.06). There were no gender differences in risk of treatment modification of the original HAART regimen during the first year of therapy for either toxicity (IRR 0.97 95% CI 0.66-1.44) or other/unknown reasons (IRR 1.18 95% CI 0.76-1.82). Finally, CD4 counts and the risk of having a detectable viral load at 1, 3 and 6 years did not differ between genders. Conclusions In a setting with free access to healthcare and HAART, gender does neither affect time from eligibility to HAART, modification of therapy nor virological and immunological response to HAART. Differences observed between genders are mainly attributable to initiation of HAART in pregnant women. PMID:23140254

  3. HIV type 1 integrase polymorphisms in treatment-naive and treatment-experienced HIV type 1-infected patients in Thailand where HIV type 1 subtype A/E predominates.

    PubMed

    Phuphuakrat, Angsana; Pasomsub, Ekawat; Kiertiburanakul, Sasisopin; Chantratita, Wasun; Sungkanuparph, Somnuek

    2012-08-01

    Integrase inhibitor (INI) is a novel antiretroviral drug recommended for both treatment-naive and treatment-experienced HIV-1-infected patients. Limited data are available on INI resistance in Thailand, where HIV-1 subtype A/E predominates. We aimed to investigate INI resistance-associated mutations (RAMs) among treatment-naive patients and patients who experienced treatment failure with NNRTI-based or PI-based antiretroviral therapy (ART) in Thailand. One hundred and eight plasma samples of 58 treatment-naive and 50 treatment-experienced HIV-1-infected individuals were collected. The HIV-1 integrase coding region was sequenced. Polymorphisms were compared between subtype A/E and B circulating in Thailand and between treatment-naive and treatment-experienced groups. Resulting amino acids were interpreted for drug resistance according to Stanford algorithms. Ninety-seven samples were HIV-1 subtype A/E, 10 were subtype B, and one was subtype C. Age, gender, and CD4 cell counts were similar between treatment-naive and treatment-experienced groups, while the treatment-failure group showed a statistically significant longer awareness time of HIV-1 infection and lower viral load than the treatment-naive group. Major INI-RAM was not found in this study, but some minor INI-RAMs, such asV54I, L68I, L74M, T97A, and S230N, were found. Comparing INI-RAMs between subtype A/E and B, the prevalence of V54I and V72I was higher in subtype B than subtype E, while V201I was found in all sequences of subtype A/E. In subtype A/E, integrase polymorphisms were not different between treatment-naive and treatment-experienced groups. However, the number of amino acid substitutions was significantly higher in the treatment-experienced group (p=0.009). One NNRTI-based ART-treated patient was found to have potential low-level INI-RAMs. INI-RAMs are rare in both treatment-naive and treatment-experienced patients in Thailand. This suggested that INI should be active in patients who are naive to

  4. Expansion in CD39⁺ CD4⁺ immunoregulatory t cells and rarity of Th17 cells in HTLV-1 infected patients is associated with neurological complications.

    PubMed

    Leal, Fabio E; Ndhlovu, Lishomwa C; Hasenkrug, Aaron M; Bruno, Fernanda R; Carvalho, Karina I; Wynn-Williams, Harry; Neto, Walter K; Sanabani, Sabri S; Segurado, Aluisio C; Nixon, Douglas F; Kallas, Esper G

    2013-01-01

    HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develops HAM/TSP. CD4⁺ T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP. The CD39 ectonucleotidase receptor is expressed on CD4⁺ T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39⁺CD25⁺) and effector (CD39⁺CD25⁻) function. Here, we investigated the expression of CD39 on CD4⁺ T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls. The frequency of CD39⁺ CD4⁺ T cells was increased in HTLV-1 infected patients, regardless of clinical status. More importantly, the proportion of the immunostimulatory CD39⁺CD25⁻ CD4⁺ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1. We saw no difference in the frequency of CD39⁺CD25⁺ regulatory (Treg) cells between AC and HAM/TSP patients. However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection. CD39⁻CD25⁺ T cell subsets predominantly secreted the inflammatory cytokine IL-17. We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4⁺ T cells compared to uninfected controls. Taken together, we show that the expression of CD39 is upregulated on CD4⁺ T cells HAM/TSP patients. This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets. CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions

  5. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial.

    PubMed

    Lawitz, Eric; Gane, Edward; Pearlman, Brian; Tam, Edward; Ghesquiere, Wayne; Guyader, Dominique; Alric, Laurent; Bronowicki, Jean-Pierre; Lester, Laura; Sievert, William; Ghalib, Reem; Balart, Luis; Sund, Fredrik; Lagging, Martin; Dutko, Frank; Shaughnessy, Melissa; Hwang, Peggy; Howe, Anita Y M; Wahl, Janice; Robertson, Michael; Barr, Eliav; Haber, Barbara

    2015-03-21

    There is a high medical need for an interferon-free, all-oral, short-duration therapy for hepatitis C virus (HCV) that is highly effective across diverse patient populations, including patients with cirrhosis or previous null response to pegylated interferon (peginterferon) plus ribavirin (PR-null responders). We aimed to assess the efficacy, safety, and effective treatment duration of grazoprevir (an HCV NS3/4A protease inhibitor) combined with elbasvir (an HCV NS5A inhibitor) with or without ribavirin in patients with HCV genotype 1 infection with baseline characteristics of poor response. The C-WORTHY trial is a randomised, open-label phase 2 trial of grazoprevir plus elbasvir with or without ribavirin; here we report findings for two cohorts of previously untreated patients with cirrhosis (cohort 1) and those with previous PR-null response with or without cirrhosis (cohort 2) enrolled in part B of the study. Eligible patients were adults aged 18 years or older with chronic HCV genotype 1 infection and HCV RNA concentrations of 10 000 IU/mL or higher in peripheral blood. We randomly assigned patients to receive grazoprevir (100 mg daily) and elbasvir (50 mg daily) with or without ribavirin for 12 or 18 weeks. Randomisation was done centrally with an interactive voice response system; patients and study investigators were masked to treatment duration up to week 12 but not to treatment allocation. The primary endpoint was the proportion of patients achieving HCV RNA less than 25 IU/mL at 12 weeks after end of treatment (SVR12), assessed by COBAS TaqMan version 2.0. This study is registered with ClinicalTrials.gov, number NCT01717326. We describe findings for 253 patients enrolled in cohort 1 (n=123) or cohort 2 (n=130). In cohort 1, we randomly assigned 60 patients to the 12-week regimen (31 with ribavirin and 29 with no ribavirin) and 63 to the 18-week regimen (32 with ribavirin and 31 with no ribavirin); in cohort 2, we randomly assigned 65 patients to the 12

  6. Finding a cure for human immunodeficiency virus-1 infection.

    PubMed

    Blankson, Joel N; Siliciano, Janet D; Siliciano, Robert F

    2014-12-01

    Remarkable advances have been made in the treatment of human immunodeficiency virus (HIV)-1 infection, but in the entire history of the epidemic, only 1 patient has been cured. Herein we review the fundamental mechanisms that render HIV-1 infection difficult to cure and then discuss recent clinical and experimental situations in which some form of cure has been achieved. Finally, we consider approaches that are currently being taken to develop a general cure for HIV-1 infection. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Early mobilization of patients receiving extracorporeal membrane oxygenation: a retrospective cohort study.

    PubMed

    Abrams, Darryl; Javidfar, Jeffrey; Farrand, Erica; Mongero, Linda B; Agerstrand, Cara L; Ryan, Patrick; Zemmel, David; Galuskin, Keri; Morrone, Theresa M; Boerem, Paul; Bacchetta, Matthew; Brodie, Daniel

    2014-02-27

    Critical illness is a well-recognized cause of neuromuscular weakness and impaired physical functioning. Physical therapy (PT) has been demonstrated to be safe and effective for critically ill patients. The impact of such an intervention on patients receiving extracorporeal membrane oxygenation (ECMO) has not been well characterized. We describe the feasibility and impact of active PT on ECMO patients. We performed a retrospective cohort study of 100 consecutive patients receiving ECMO in the medical intensive care unit of a university hospital. Of the 100 patients receiving ECMO, 35 (35%) participated in active PT; 19 as bridge to transplant and 16 as bridge to recovery. Duration of ECMO was 14.3 ± 10.9 days. Patients received 7.2 ± 6.5 PT sessions while on ECMO. During PT sessions, 18 patients (51%) ambulated (median distance 175 feet, range 4 to 2,800) and 9 patients were on vasopressors. Whilst receiving ECMO, 23 patients were liberated from invasive mechanical ventilation. Of the 16 bridge to recovery patients, 14 (88%) survived to discharge; 10 bridge to transplant patients (53%) survived to transplantation, with 9 (90%) surviving to discharge. Of the 23 survivors, 13 (57%) went directly home, 8 (35%) went to acute rehabilitation, and 2 (9%) went to subacute rehabilitation. There were no PT-related complications. Active PT, including ambulation, can be achieved safely and reliably in ECMO patients when an experienced, multidisciplinary team is utilized. More research is needed to define the barriers to PT and the impact on survival and long-term functional, neurocognitive outcomes in this population.

  8. Decreased Specificity of an Assay for Recent Infection in HIV-1-Infected Patients on Highly Active Antiretroviral Treatment: Implications for Incidence Estimates

    PubMed Central

    Chaillon, Antoine; Le Vu, Stéphane; Brunet, Sylvie; Gras, Guillaume; Bastides, Frédéric; Bernard, Louis; Meyer, Laurence

    2012-01-01

    The aim of this study was to estimate the rate of misclassification in treated HIV patients who initiated treatment at the chronic stage of HIV infection using an enzyme immunoassay (EIA) that discriminates between recent infection (RI; within 6 months) and established infection. The performance of EIA-RI was evaluated in 96 HIV-1 chronically infected patients on highly active antiretroviral therapy (HAART) with an undetectable viral load (VL) for at least 3 years. Demographic data, HIV-1 viral load, CD4+ T-cell count, viral subtype, and treatment duration were collected. The subset of misclassified patients was further analyzed using samples collected annually. The impact on incidence estimates was evaluated by simulation. The specificity in treated patients was significantly lower (70.8 to 77.1%) than that observed in untreated patients (93.3 to 99.3%, P < 0.001). Patients falsely classified as recently infected had been treated for a longer period and had longer-term viral suppression than those correctly classified. The loss of specificity of the test due to treatment may have a dramatic impact on the accuracy of the incidence estimates, with a major impact when HIV prevalence is high. The cross-sectional studies intended to derive HIV incidence must collect information on treatment or, alternatively, should include detection of antiretroviral drugs in blood specimens to rule out treated patients from the calculations. PMID:22718132

  9. Perturbation and Nonlinear Dynamic Analysis of Acoustic Phonatory Signal in Parkinsonian Patients Receiving Deep Brain Stimulation

    ERIC Educational Resources Information Center

    Lee, Victoria S.; Zhou, Xiao Ping; Rahn, Douglas A., III; Wang, Emily Q.; Jiang, Jack J.

    2008-01-01

    Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D[subscript 2]), percent jitter, percent shimmer,…

  10. Perturbation and Nonlinear Dynamic Analysis of Acoustic Phonatory Signal in Parkinsonian Patients Receiving Deep Brain Stimulation

    ERIC Educational Resources Information Center

    Lee, Victoria S.; Zhou, Xiao Ping; Rahn, Douglas A., III; Wang, Emily Q.; Jiang, Jack J.

    2008-01-01

    Nineteen PD patients who received deep brain stimulation (DBS), 10 non-surgical (control) PD patients, and 11 non-pathologic age- and gender-matched subjects performed sustained vowel phonations. The following acoustic measures were obtained on the sustained vowel phonations: correlation dimension (D[subscript 2]), percent jitter, percent shimmer,…

  11. Sex differences in chronic pain management practices for patients receiving opioids from the Veterans Health Administration.

    PubMed

    Oliva, Elizabeth M; Midboe, Amanda M; Lewis, Eleanor T; Henderson, Patricia T; Dalton, Aaron L; Im, Jinwoo J; Seal, Karen; Paik, Meenah C; Trafton, Jodie A

    2015-01-01

    Women experience chronic pain and use pain-related health care at higher rates than men. It is not known whether the pain-related health care female veterans receive is consistent with clinical practice guideline recommendations or whether receipt of this care differs between men and women. The aim of this study was to identify whether sex differences in chronic pain management care exist for patients served by the Veterans Health Administration (VHA). Data on patient demographics, diagnostic criteria, and health care utilization were extracted from VHA administrative databases for fiscal year 2010 (FY10). Patients in this study included all VHA patients (excluding metastatic cancer patients) who received more than 90 days of a short-acting opioid medication or a long-acting opioid medication prescription in FY10 study. Multilevel logistic regressions were conducted to identify sex differences in receipt of guideline-recommended chronic pain management. A total of 480,809 patients met inclusion criteria. Female patients were more likely to receive most measures of guideline-recommended care for chronic pain including mental health assessments, psychotherapy, rehabilitation therapy, and pharmacy reconciliation. However, women were more likely to receive concurrent sedative prescriptions, which is inconsistent with guideline recommendations. Most of the observed sex differences persisted after controlling for key demographic and diagnostic differences. Findings suggest that female VHA patients are more likely to receive an array of pain management practices than male patients, including both contraindicated and recommended polypharmacy. Quality improvement efforts to address underutilization of mental health and rehabilitative services for pain by male patients and polypharmacy in female patients should be considered. Wiley Periodicals, Inc.

  12. Adequacy of treatment received by primary care patients with anxiety disorders.

    PubMed

    Weisberg, Risa B; Beard, Courtney; Moitra, Ethan; Dyck, Ingrid; Keller, Martin B

    2014-05-01

    We examined the adequacy of pharmacotherapy and psychotherapy received by primary care patients with anxiety disorders over up to 5 years of follow-up. Five hundred thirty-four primary care patients at 15 US sites, who screened positive for anxiety symptoms, were assessed for anxiety disorders. Those meeting anxiety disorder criteria were offered participation and interviewed again at six and 12 months postintake, and yearly thereafter for up to 5 years. We utilized existing definitions of appropriate pharmacotherapy and created definitions of potentially adequate psychotherapy/cognitive-behavioral therapy (CBT). At intake, of 534 primary care participants with anxiety disorders, 19% reported receiving appropriate pharmacotherapy and 14% potentially adequate CBT. Overall, 28% of participants reported receiving potentially adequate anxiety treatment, whether pharmacotherapy, psychotherapy, or both. Over up to five years of follow-up, appropriate pharmacotherapy was received by 60% and potentially adequate CBT by 36% of the sample. Examined together, 69% of participants received any potentially adequate treatment during the follow-up period. Over the course of follow-up, primary care patients with MDD, panic disorder with agoraphobia, and with medicaid/medicare were more likely to receive appropriate anxiety treatment. Ethnic minority members were less likely to receive potentially adequate care. Potentially adequate anxiety treatment was rarely received by primary care patients with anxiety disorders at intake. Encouragingly, rates improved over the course of the study. However, potentially adequate CBT remained much less utilized than pharmacotherapy and racial-ethnic minority members were less likely to received care, suggesting much room for improved dissemination of quality treatment. © 2013 Wiley Periodicals, Inc.

  13. ADEQUACY OF TREATMENT RECEIVED BY PRIMARY CARE PATIENTS WITH ANXIETY DISORDERS

    PubMed Central

    Weisberg, Risa B.; Beard, Courtney; Moitra, Ethan; Dyck, Ingrid; Keller, Martin B.

    2014-01-01

    Background We examined the adequacy of pharmacotherapy and psychotherapy received by primary care patients with anxiety disorders over up to 5 years of follow-up. Method Five hundred thirty-four primary care patients at 15 US sites, who screened positive for anxiety symptoms, were assessed for anxiety disorders. Those meeting anxiety disorder criteria were offered participation and interviewed again at six and 12 months postintake, and yearly thereafter for up to 5 years. We utilized existing definitions of appropriate pharmacotherapy and created definitions of potentially adequate psychotherapy/cognitive-behavioral therapy (CBT). Results At intake, of 534 primary care participants with anxiety disorders, 19% reported receiving appropriate pharmacotherapy and 14% potentially adequate CBT. Overall, 28% of participants reported receiving potentially adequate anxiety treatment, whether pharmacotherapy, psychotherapy, or both. Over up to five years of follow-up, appropriate pharmacotherapy was received by 60% and potentially adequate CBT by 36% of the sample. Examined together, 69% of participants received any potentially adequate treatment during the follow-up period. Over the course of follow-up, primary care patients with MDD, panic disorder with agoraphobia, and with medicaid/medicare were more likely to receive appropriate anxiety treatment. Ethnic minority members were less likely to receive potentially adequate care. Conclusions Potentially adequate anxiety treatment was rarely received by primary care patients with anxiety disorders at intake. Encouragingly, rates improved over the course of the study. However, potentially adequate CBT remained much less utilized than pharmacotherapy and racial-ethnic minority members were less likely to received care, suggesting much room for improved dissemination of quality treatment. PMID:24190762

  14. Methemoglobinemia in a Pediatric Oncology Patient Receiving Sulfamethoxazole/Trimethoprim Prophylaxis.

    PubMed

    Carroll, Timothy G; Carroll, Megan G

    2016-07-18

    BACKGROUND Methemoglobinemia due to the administration of sulfamethoxazole/trimethoprim has been documented in a series of case reports. However, all of these reports are on adult patients, and all patients received at least daily administration of sulfamethoxazole/trimethoprim for the treatment of active or suspected infection. CASE REPORT Herein we report the development of methemoglobinemia in a pediatric patient receiving sulfamethoxazole/trimethoprim three times weekly for the prophylaxis of opportunistic infections. CONCLUSIONS The clinician should always consider sulfamethoxazole/trimethoprim, even when administered for opportunistic infection prophylaxis at reduced doses and intervals, as a possible cause of methemoglobinemia.

  15. Leukoencephalopathy in small cell lung cancer patients receiving prophylactic cranial irradiation

    SciTech Connect

    Frytak, S.; Shaw, J.N.; O'Neill, B.P.; Lee, R.E.; Eagan, R.T.; Shaw, E.G.; Richardson, R.L.; Coles, D.T.; Jett, J.R.

    1989-02-01

    The cases of 283 small cell lung cancer patients who received treatment with combination chemotherapy with or without prophylactic cranial irradiation (PCI) were reviewed to determine the incidence of leukoencephalopathy. The overall incidence was 10%. Of all patients receiving PCI, 17% developed neurotoxicity, and of those receiving PCI and surviving greater than or equal to 1.5 years, 37% suffered neurologic sequelae. In those receiving PCI but surviving less than 1.5 years, the incidence of neurotoxicity was 4%. The mean time interval between the end of PCI and the onset of neurotoxicity was 17 months (range 2-63 months). The PCI dose ranged from 2600-3600 cGy. None of the patients not receiving PCI developed neurotoxicity. The incidence of neurotoxicity in long-term survivors (greater than or equal to 1.5 years) with respect to PCI dose was less than or equal to 3000 cGy (25%), 3200 cGy (56%), 3600 cGy (36%). Almost all of the patients getting PCI also received lomustine, an agent associated with DNA repair inhibition and synergism with DNA damaging agents such as ionizing radiation or alkylating agents. Under the conditions of our study, PCI was associated with an unacceptable risk of neurotoxicity. Until further information is forthcoming, one should proceed with caution when using PCI in conjunction with lomustine.

  16. HIV-1 drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Asia: results from the TREAT Asia Studies to Evaluate Resistance-Monitoring Study.

    PubMed

    Sungkanuparph, Somnuek; Oyomopito, Rebecca; Sirivichayakul, Sunee; Sirisanthana, Thira; Li, Patrick C K; Kantipong, Pacharee; Lee, Christopher K C; Kamarulzaman, Adeeba; Messerschmidt, Liesl; Law, Matthew G; Phanuphak, Praphan

    2011-04-15

    Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.

  17. Cost-effectiveness of all-oral ledipasvir/sofosbuvir regimens in patients with chronic hepatitis C virus genotype 1 infection.

    PubMed

    Younossi, Z M; Park, H; Saab, S; Ahmed, A; Dieterich, D; Gordon, S C

    2015-03-01

    An all-oral, pegylated interferon (pegIFN)-free and ribavirin (RBV)-free single-tablet of ledipasvir (LDV) and sofosbuvir (SOF) is now approved for the treatment of patients infected with hepatitis C virus (HCV) genotype 1. To estimate the health economic outcomes for LDV/SOF compared with current treatments in US patients infected with HCV genotype 1. A hybrid decision-tree and Markov state-transition model was developed. For a cohort of 10,000 patients, the model captured outcomes for several pairings of LDV/SOF with comparators, including long-term health outcomes, number need to treat, life-years gained, quality-adjusted life-years (QALYS) gained, incremental cost-effectiveness ratios and costs per sustained virologic response (SVR). Patients with different levels of treatment experience and different cirrhosis stages were included. LDV/SOF decreased the number of advanced liver disease cases by 0-93% compared with current regimens or no treatment in treatment-naïve patients. In treatment-experienced [pegIFN plus ribavirin (PR) or protease inhibitor (PI) + PR] patients, treatment with LDV/SOF decreased the incidence of advanced liver disease complications in most of the cases analysed, except SOF + SMV. For all patient sub-cohorts, LDV/SOF was associated with the lowest 1-year costs per SVR and, with regard to lifetime incremental costs per QALY gained, was either dominant or the most cost-effective treatment. Overall, treatment initiation at earlier stages of liver fibrosis resulted in improved health economic outcomes. LDV/SOF is associated with more favourable short- and long-term health economic outcomes compared with current therapies for patients across all levels of treatment experience and cirrhosis stages. © 2015 John Wiley & Sons Ltd.

  18. Reduction in diarrhea incidence by soluble fiber in patients receiving total or supplemental enteral nutrition.

    PubMed

    Homann, H H; Kemen, M; Fuessenich, C; Senkal, M; Zumtobel, V

    1994-01-01

    Gastrointestinal side effects, particularly diarrhea, are still the main reasons for discontinuation of enteral nutrition. Although the causes of diarrhea are diverse, the enteral nutrition solution is frequently suspected of playing a leading role in causing diarrhea. Our randomized, prospective, double-blind trial with 100 patients assessed the effects of feeding a standard diet (Nutrodrip Standard) vs the same diet supplemented with 20 g of soluble fiber, containing partially hydrolyzed guar gum (Sunfiber), per 1000 mL. Thirty patients received total enteral nutrition postoperatively, and 70 patients received enteral supplementation. The patients receiving total enteral nutrition with soluble fiber had decreased diarrhea but increased flatulence. In none of these patients did enteral feeding have to be discontinued because of gastrointestinal side effects, whereas in four patients who were on a standard diet, enteral feeding had to be interrupted because of diarrhea (p < .05). Similar observations were made in patients receiving enteral supplementation. In both groups, the incidence of diarrhea decreased significantly with the soluble fiber diet compared with the standard diet (6 vs 15, p < .05). Enteral feeding with a formula supplemented with partially hydrolyzed guar gum reduces the incidence of diarrhea in patients receiving total enteral nutrition as well as in those receiving enteral supplementation, regardless of the cause of diarrhea. The increased hydrogen production and the significantly higher rate of flatulence are likely to result from fermentation of the soluble fiber in the colon, with concomitant production of short-chain fatty acids, which leads to increased absorption of short-chain fatty acids, sodium, and water by the colonocytes. This effect, together with the observed cholecystokinin-mediated decrease in colonic transit time with partially hydrolyzed guar gum, may explain the reduction in the incidence of diarrhea in this study.

  19. Colon Cancer Screening among Patients Receiving Dialysis in the United States: Are We Choosing Wisely?

    PubMed

    Carlos, Christopher A; McCulloch, Charles E; Hsu, Chi-Yuan; Grimes, Barbara; Pavkov, Meda E; Burrows, Nilka R; Shahinian, Vahakn B; Saran, Rajiv; Powe, Neil R; Johansen, Kirsten L

    2017-08-01

    The American Society of Nephrology recommends against routine cancer screening among asymptomatic patients receiving maintenance dialysis on the basis of limited survival benefit. To determine the frequency of colorectal cancer screening among patients on dialysis and the extent to which screening tests were targeted toward patients at lower risk of death and higher likelihood of receiving a kidney transplant, we performed a cohort study of 469,574 Medicare beneficiaries ages ≥50 years old who received dialysis between January 1, 2007 and September 30, 2012. We examined colorectal cancer screening tests according to quartiles of risk of mortality and kidney transplant on the basis of multivariable Cox modeling. Over a median follow-up of 1.5 years, 11.6% of patients received a colon cancer screening test (57.9 tests per 1000 person-years). Incidence rates of colonoscopy, flexible sigmoidoscopy, and fecal occult blood test were 27.9, 0.6, and 29.5 per 1000 person-years, respectively. Patients in the lowest quartile of mortality risk were more likely to be screened than those in the highest quartile (hazard ratio, 1.53; 95% confidence interval, 1.49 to 1.57; 65.1 versus 46.4 tests per 1000 person-years, respectively), amounting to a 33% higher rate of testing. Additionally, compared with patients least likely to receive a transplant, patients most likely to receive a transplant were more likely to be screened (hazard ratio, 1.68; 95% confidence interval, 1.64 to 1.73). Colon cancer screening is being targeted toward patients on dialysis at lowest risk of mortality and highest likelihood of transplantation, but absolute rates are high, suggesting overscreening. Copyright © 2017 by the American Society of Nephrology.

  20. Peripheral Blood Cytotoxic γδ T Lymphocytes from Patients with Human Immunodeficiency Virus Type 1 Infection and AIDS Lyse Uninfected CD4+ T Cells, and Their Cytocidal Potential Correlates with Viral Load

    PubMed Central

    Sindhu, Sardar T. A. K.; Ahmad, Rasheed; Morisset, Richard; Ahmad, Ali; Menezes, José

    2003-01-01

    Progression of human immunodeficiency virus type 1 (HIV-1) infection in humans is marked by declining CD4+-T-cell counts and increasing virus load (VL). Cytotoxic T lymphocytes (CTL) play an important role in the lysis of HIV-infected cells, especially during the early phase of asymptomatic infection. CTL responses in the later phase of disease progression may not be as effective since progressors with lower CD4+-T-cell counts have consistently higher VL despite having elevated CTL counts. We hypothesized that, apart from antiviral effects, some CTL might also contribute to AIDS pathogenesis by depleting CD4+ T cells and that this CTL activity may correlate with the VL in AIDS patients. Therefore, a cross-sectional study of 31 HIV-1-infected patients at various clinical stages was carried out. Purified CTL from these donors as well as HIV-seronegative controls were used as effectors against different human cell targets by using standard 51Cr release cytolytic assays. A direct correlation between VL and CTL-mediated, major histocompatibility complex (MHC)-unrestricted lysis of primary CD4+-T-cell, CEM.NKR, and K562 targets was observed. CD4+-T-cell counts and duration of infection also correlated with MHC-unrestricted cytolytic activity. Our data clearly show that γδ CTL are abnormally expanded in the peripheral blood of HIV-infected patients and that the Vδ1 subset of γδ T cells is the main effector population responsible for this type of cytolysis. The present data suggest that γδ CTL can contribute to the depletion of bystander CD4+ T cells in HIV-infected patients as a parallel mechanism to HIV-associated immunopathogenesis and hence expedite AIDS progression. PMID:12525619

  1. Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study.

    PubMed

    Callefi, Luciana Azevedo; Villela-Nogueira, Cristiane Alves; de Barros Tenore, Simone; Carnaúba-Júnior, Dimas; Coelho, Henrique Sérgio Moraes; Pinto, Paulo de Tarso A; Nabuco, Letícia Cancella; Pessoa, Mário Guimarães; Ferraz, Maria Lucia Cardoso Gomes; Ferreira, Paulo Roberto Abrão; de Lourdes Candolo Martinelli, Ana; Chachá, Silvana Gama Florencio; de Souza Paiva Ferreira, Adalgisa; de Macedo Bisio, Alessandra Porto; Brandão-Mello, Carlos Eduardo; Álvares-Da-Silva, Mário Reis; Reuter, Tânia; Ivantes, Claudia Alexandra Pontes; de Mello Perez, Renata; Mendes-Correa, Maria Cássia Jacintho

    2017-06-01

    To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

  2. The effectiveness of scalp cooling in preventing alopecia for patients receiving epirubicin and docetaxel.

    PubMed

    Macduff, C; Mackenzie, T; Hutcheon, A; Melville, L; Archibald, H

    2003-06-01

    The aim of this study was to establish the effectiveness of scalp cooling in preventing alopecia for patients with breast cancer who received the trial combination chemotherapy of Epirubicin and Docetaxel. Doubt remains about the general effectiveness of scalp cooling in preventing hair loss for patients receiving chemotherapy. There is very little information available about its specific effectiveness with combinations of Taxanes and Anthracycline drugs. Of the 40 patients who received this drug combination, 10 were included in a pilot study whereas the remaining 30 constituted the main study sample. A randomized controlled study was undertaken whereby the intervention group received scalp cooling via gel cool caps and the control group received no specific preventative intervention. Nurses assessed participants' hair loss using a modified version of the WHO scale at seven time points and also recorded hair loss photographically. Two independent experts rated the photographs using the same scale. Patients self-reported in relation to overall hair loss, hair condition, levels of emotional upset, negativity about appearance, hair re-growth and wig use. Significantly greater hair loss was apparent in the control group during most of the treatment period. However, the level of protection afforded by the cool caps was relatively poor with this chemotherapy combination. The marginal benefits of scalp cooling in this context must be clearly explained to patients.

  3. Haemoglobin recovery among HIV-1 infected patients on zidovudine-based antiretroviral therapy and other regimens in north-central Nigeria.

    PubMed

    Parrish, Deidra D; Blevins, Meridith; Megazzini, Karen M; Shepherd, Bryan E; Mohammed, Mukhtar Y; Wester, C William; Vermund, Sten H; Aliyu, Muktar H

    2014-04-01

    We conducted a study to assess trends in haemoglobin recovery among HIV-infected patients initiated on zidovudine-based combination antiretroviral therapy (cART) stratified by baseline haemoglobin level. Haemoglobin data from non-pregnant adult patients initiating cART in rural north-central Nigeria between June 2009 and May 2011 were analysed using a linear mixed effects model to assess the interaction between time, zidovudine-containing regimen and baseline haemoglobin level on the outcome of subsequent haemoglobin level. Best-fit curves were created for baseline haemoglobin in the 10th, 25th, 75th and 90th percentiles. We included 313 patients with 736 measures of haemoglobin in the analysis (239 on zidovudine and 74 on non-zidovudine-containing regimens). Median haemoglobin increased over time in both groups, with differences in haemoglobin response over time related to baseline haemoglobin levels and zidovudine use (p = 0.003). The groups of patients on zidovudine at the 10th and 90th percentiles had downward sloping curves while all other groups had upward trending haemoglobin levels. Although haemoglobin levels increased overall for patients on zidovudine-containing regimens, for those in the 10th and 90th percentiles haemoglobin levels trended downward over time. These results have implications for decisions regarding when to initiate, switch from or avoid the use of zidovudine.

  4. Hemoglobin recovery among HIV-1 infected patients on zidovudine-based antiretroviral therapy and other regimens in North-central Nigeria

    PubMed Central

    Parrish, Deidra D.; Blevins, Meridith; Megazzini, Karen M.; Shepherd, Bryan E.; Mohammed, Mukhtar Y.; Wester, C William; Vermund, Sten H.; Aliyu, Muktar H.

    2015-01-01

    Objective To assess trends in hemoglobin recovery among HIV-infected patients initiated on zidovudine-based combined antiretroviral therapy (cART) stratified by baseline hemoglobin level. Methods Hemoglobin data from non-pregnant adult patients initiating cART in rural north-central Nigeria between June 2009 and May 2011 was analyzed using a linear mixed effects model to assess the interaction between time, zidovudine-containing regimen, and baseline hemoglobin level on the outcome of subsequent hemoglobin level. Best fit curves were created for baseline hemoglobin in the 10th, 25th, 75th and 90th percentiles. Results We included 313 patients with 736 measures of hemoglobin in the analysis (239 on zidovudine and 74 on non-zidovudine-containing regimens). Median hemoglobin increased over time in both groups, with differences in hemoglobin response over time related to baseline hemoglobin levels and zidovudine use (p = 0.003). The groups of patients on zidovudine at the 10th and 90th percentiles had downward sloping curves while all other groups had upward trending hemoglobin levels. Conclusion Though hemoglobin levels increased overall for patients on zidovudine-containing regimens, for those in the 10th and 90th percentiles hemoglobin levels trended downward over time. These results have implications for decisions regarding when to initiate, switch from or avoid the use of zidovudine. PMID:24104694

  5. Pre-existence and Persistence of Resistant Minority Hepatitis C Virus Variants in Genotype 1-Infected Patients Treated With Simeprevir/Peginterferon/Ribavirin.

    PubMed

    Fevery, Bart; Thys, Kim; Van Eygen, Veerle; Verbinnen, Thierry; Van Rossem, Elizabeth; Buelens, Annemie; Aerssens, Jeroen; Witek, James; Picchio, Gaston; De Meyer, Sandra; Lenz, Oliver

    2016-03-01

    Background.  The pre-existence of minority hepatitis C virus (HCV) variants and their impact on treatment outcome, as well as the persistence of emerging resistant variants posttreatment in patients failing treatment with simeprevir/peginterferon/ribavirin (SMV/PR), were assessed by deep sequencing (DS). Methods.  Population sequencing (PS) and Illumina DS were performed on HCV genotype 1 isolates from patients treated with SMV/PR in Phase 2b (PILLAR [NCT00882908] and ASPIRE [NCT00980330]) and Phase 3 (QUEST-1 [NCT01289782], QUEST-2 [NCT01290679], and PROMISE [NCT01281839]) trials. Results.  Minority polymorphisms (ie, detected pretreatment by DS only) reducing SMV activity in vitro were uncommon (3.6%, 19 of 534 patients). These SMV-resistant minority polymorphisms were detected in similar proportions of patients achieving (3.7%) and not achieving (3.3%) sustained virologic response with SMV/PR and generally did not emerge as major variants at time of failure. SMV-resistant variants emerging at time of failure were no longer detected at end of study in 69.3% and 52.0% of the patients by PS and DS, respectively. Conclusions.  Minority polymorphisms did not impact outcome of SMV/PR treatment. The majority of emerging variants that became undetectable at end of study by PS were also undetectable by DS. These results suggest no added value of DS for clinical usage of SMV.

  6. Clinical outcome in patients with venous thromboembolism receiving concomitant anticoagulant and antiplatelet therapy.

    PubMed

    Tzoran, Inna; Brenner, Benjamin; Sakharov, Gleb; Trujillo-Santos, Javier; Lorenzo, Alicia; Madridano, Olga; López-Sáez, Juan Bosco; Monreal, Manuel

    2014-11-01

    Patients with arterial disease receiving antiplatelet agents may develop venous thromboembolism (VTE) and need anticoagulant therapy, although concomitant use of these drugs may increase bleeding risk. We analyzed RIETE data and compared clinical outcomes depending on decision to discontinue or maintain antiplatelet therapy at VTE diagnosis. Consecutive patients with acute VTE were enrolled in RIETE. Only patients receiving antiplatelet therapy at baseline were included in this analysis. Primary outcomes were: rate of subsequent ischemic events, major bleeding or death during anticoagulation course. 1178 patients who received antiplatelet drugs at VTE diagnosis were included. Antiplatelet therapy was discontinued in 62% of patients. During anticoagulation course, patients also receiving antiplatelet therapy had higher rates of lower limb amputations (2.28 vs. 0.21 events per 100 patients-years; p<0.01), any ischemic events (5.7 vs. 2.28 events per 100 patients-years; p<0.05) or death (23.6 vs. 13.9 deaths per 100 patients-years; p<0.01). No differences in the rate of major bleeding or recurrent VTE were revealed. In matched analysis, patients on antiplatelet therapy were found to have a significantly higher rate of limb amputations (odds ratio: 15.3; 95% CI: 1.02-229) and an increased number of composite outcomes including all-cause deaths, arterial and VTE events (odds ratio: 1.46; CI: 1.03-2.06), with no differences in major bleeding rate. Concomitant anticoagulant and antiplatelet therapy in patients with VTE and arterial disease is not associated with increased risk for bleeding, recurrent VTE or death. The worse outcome observed in patients who continued antiplatelet therapy requires further investigations. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  7. Predicting and preventing thromboembolic events in patients receiving cisplatin-based chemotherapy for germ cell tumours.

    PubMed

    Gizzi, Marco; Oberic, Lucie; Massard, Christophe; Poterie, Audrey; Gwenael, Le Teuff; Loriot, Yohann; Albiges, Laurence; Baciarello, Giulia; Michels, Judith; Bossi, Alberto; Blanchard, Pierre; Escudier, Bernard; Fizazi, Karim

    2016-12-01

    Patients with germ cell tumours (GCT) receiving cisplatin-based chemotherapy are at high risk of thromboembolic events (TEE). Previously, we identified serum lactate dehydrogenase (LDH) and body surface area (BSA) as independent predictive factors for TEE. The aim of this study was to validate these predictive factors and to assess the impact of thromboembolism prophylaxis in patients at risk of deep venous thrombosis (DVT). Between 2001 and 2014, 295 patients received first-line cisplatin-based chemotherapy for GCT. Preventive anticoagulation with low-molecular-weight heparin (LMWH) was progressively implemented in patients with predictive factors. Sixteen patients with evidence of TEE before starting chemotherapy were excluded from the analysis. Among 279 eligible patients, a TEE occurred in 38 (14%) consisting of DVT (n = 26), arterial thrombosis (n = 2), and superficial thrombophlebitis (n = 10). DVT occurred in 26 (12.7%) of 204 patients with risk factors versus two (2.6%) of 75 patients with no risk factors (p = 0.01). After a prevention protocol was progressively implemented from 2005, primary thromboprophylaxis was administered to 104 patients (68%) with risk factors. Among patients at risk (n = 151), the incidence of DVT decreased by roughly half when they received a LMWH: 9/97 (9.2%) and 9/54 (16.6%), respectively (p = 0.23). Patients with GCT who receive cisplatin-based chemotherapy are at risk of developing a TEE which can be predicted by elevated serum LDH. To our knowledge this is the first study exploring LMWH as thromboprophylaxis in GCT patients. A prospective trial testing prophylactic anticoagulation is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Osteonecrosis of the jaw in patients with cancer who received zoledronic acid and bevacizumab.

    PubMed

    Francini, Filippo; Pascucci, Alessandra; Francini, Edoardo; Miano, Salvatora Tindara; Bargagli, Gianluca; Ruggiero, Grazia; Petrioli, Roberto

    2011-05-01

    The authors investigated the incidence of and risk factors for osteonecrosis of the jaw (ONJ) in patients with metastases to the bone who received the bisphosphonate agent zoledronic acid (ZOL) and chemotherapy combined with the antiangiogenic agent bevacizumab (BEV). The authors evaluated 59 participants (34 with breast cancer and 25 with nonsmall-cell lung cancer). All of the participants received 4 milligrams of ZOL via intravenous (IV) infusion every four weeks and 15 mg per kilogram of BEV every three weeks. They conducted a dental examination in participants at baseline and every three months until the patients died or were lost to follow-up. If needed, participants received periodontal disease treatment and underwent tooth extraction before they started receiving ZOL and BEV. The median time the participants received ZOL therapy was 18.8 months (range, 3.1-28.9 months); 36 participants (61.0 percent) received ZOL therapy for more than one year. The median time participants received BEV therapy was 16.7 months (range, 2.8-29.6 months). None of the participants required dentoalveolar surgery while undergoing cancer treatment. After a median follow-up period of 19.7 months, none of the participants developed bisphosphonate-related ONJ. ZOL combined with BEV did not predispose to ONJ participants with cancer that had metastasized to the bone who underwent a baseline dental examination and preventive dental measures. The study results must be considered in the context of the study's protocols and the follow-up period.

  9. CD4+ T cell depletion in an untreated HIV type 1-infected human leukocyte antigen-B*5801-positive patient with an undetectable viral load.

    PubMed

    Andrade, Adriana; Bailey, Justin R; Xu, Jie; Philp, Frances H; Quinn, Thomas C; Williams, Thomas M; Ray, Stuart C; Thomas, David L; Blankson, Joel N

    2008-04-15

    We report a case of a patient infected with human immunodeficiency virus type 1 (HIV-1) for 20 years who has experienced CD4(+) T cell depletion in spite of maintaining undetectable viral loads. Our data suggest that immune activation can cause CD4(+) T cell depletion even when HIV-1 replication appears to be controlled by host factors.

  10. Long-term efficacy and safety of etravirine-containing regimens in a real-life cohort of treatment-experienced HIV-1-infected patients.

    PubMed

    Allavena, Clotilde; Katlama, Christine; Cotte, Laurent; Roger, Pierre Marie; Delobel, Pierre; Cheret, Antoine; Duvivier, Claudine; Poizot-Martin, Isabelle; Hoen, Bruno; Cabie, André; Cheret, Arnaud; Lahoulou, Rima; Raffi, François; Pugliese, Pascal

    2016-01-01

    Etravirine (ETR) was approved in France in September 2008 and is used in combination with a boosted protease inhibitor (bPI) and other anti-retrovirals (ART) in HIV-infected pre-treated patients. This study aimed to report in a real-life setting the efficacy and tolerability of ETR-based regimens and factors associated with virological response. The study population included all treatment-experienced patients who initiated an ETR-based regimen between September 2008 and July 2013 from the French Dat'AIDS cohort. Analyses were performed in ART-experienced patients starting ETR after virological failure (VF) or as a maintenance therapy (MT), with or without bPI. A total of 2006 patients (VF, n = 1014 (51%); MT, n = 992 (49%)) were included. At M12, the proportion of patients with HIV RNA < 50 copies/ml was 71.7% (72.0% and 71.1% with or without bPI) in the VF group and 90.5% (85.0% and 92.3% with or without bPI) in the MT group, without significant differences regarding the use of bPI. ETR was discontinued in 8.8% of patients for adverse events in 23.9% of cases (21.5% in VF, 29.5% in MT), treatment failure in 15.2% (16.2% in VF, 7.4% in MT) or simplification in 5.4% (4.6% in VF, 7.4% in MT). In the VF group, factors associated with virological response were a longer duration of HIV infection (OR = 2.7; p < 0.001) and baseline HIV RNA < 5 log10 copies/mL (OR = 2.1; p = 0.002). This study shows that in ART-experienced patients ETR is well tolerated with a high efficacy when combined with other active drugs, even when the regimen does not include a bPI.

  11. DISCORDANCE BETWEEN BODY MASS INDEX AND ANTHROPOMETRIC MEASUREMENTS AMONG HIV-1-INFECTED PATIENTS ON ANTIRETROVIRAL THERAPY AND WITH LIPOATROPHY/LIPOHYPERTROPHY SYNDROME

    PubMed Central

    SOARES, Lismeia Raimundo; da SILVA, Daniela Cardeal; GONSALEZ, Claudio R.; BATISTA, Felipe G.; FONSECA, Luiz Augusto M.; DUARTE, Alberto J.S.; CASSEB, Jorge

    2015-01-01

    Introduction: Highly Active Antiretroviral Therapy (HAART) has improved and extended the lives of thousands of people living with HIV/AIDS around the world. However, this treatment can lead to the development of adverse reactions such as lipoatrophy/lipohypertrophy syndrome (LLS) and its associated risks. Objective: This study was designed to assess the prevalence of self-reported lipodystrophy and nutritional status by anthropometric measurements in patients with HIV/AIDS. Methods: An observati