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Sample records for nonresponders hiv-coinfected patients

  1. HBV/HIV coinfection is associated with poorer outcomes in hospitalized patients with HBV or HIV.

    PubMed

    Rajbhandari, R; Jun, T; Khalili, H; Chung, R T; Ananthakrishnan, A N

    2016-10-01

    We examined the impact of HBV/HIV coinfection on outcomes in hospitalized patients compared to those with HBV or HIV monoinfection. Using the 2011 US Nationwide Inpatient Sample, we identified patients who had been hospitalized with HBV or HIV monoinfection or HBV/HIV coinfection using ICD-9-CM codes. We compared liver-related admissions between the three groups. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality, length of stay and total charges. A total of 72 584 discharges with HBV monoinfection, 133 880 discharges with HIV monoinfection and 8156 discharges with HBV/HIV coinfection were included. HBV/HIV coinfection was associated with higher mortality compared to HBV monoinfection (OR 1.67, 95% CI 1.30-2.15) but not when compared to HIV monoinfection (OR 1.22, 95% CI 0.96-1.54). However, the presence of HBV along with cirrhosis or complications of portal hypertension was associated with three times greater in-hospital mortality in patients with HIV compared to those without these complications (OR 3.00, 95% CI 1.80-5.02). Length of stay and total hospitalization charges were greater in the HBV-/HIV-coinfected group compared to the HBV monoinfection group (+1.53 days, P < 0.001; $17595, P < 0.001) and the HIV monoinfection group (+0.62 days, P = 0.034; $8840, P = 0.005). In conclusion, HBV/HIV coinfection is a risk factor for in-hospital mortality, particularly in liver-related admissions, compared to HBV monoinfection. Overall healthcare utilization from HBV/HIV coinfection is also higher than for either infection alone and higher than the national average for all hospitalizations, thus emphasizing the healthcare burden from these illnesses. © 2016 John Wiley & Sons Ltd.

  2. HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis.

    PubMed

    Pineda, Juan A; Romero-Gómez, Manuel; Díaz-García, Fernando; Girón-González, José A; Montero, José L; Torre-Cisneros, Julián; Andrade, Raúl J; González-Serrano, Mercedes; Aguilar, José; Aguilar-Guisado, Manuela; Navarro, José M; Salmerón, Javier; Caballero-Granado, Francisco J; García-García, José A

    2005-04-01

    The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.

  3. Anti-TB drug concentrations and drug-associated toxicities among TB/HIV-coinfected patients.

    PubMed

    Sekaggya-Wiltshire, C; von Braun, A; Scherrer, A U; Manabe, Y C; Buzibye, A; Muller, D; Ledergerber, B; Gutteck, U; Corti, N; Kambugu, A; Byakika-Kibwika, P; Lamorde, M; Castelnuovo, B; Fehr, J; Kamya, M R

    2017-04-01

    Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations. Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median C max of 6.57 (IQR 4.83-9.41) μg/mL, 7.39 (IQR 5.10-10.20) μg/mL, 7.00 (IQR 6.05-10.95) μg/mL and 3.86 (IQR 2.81-14.24) μg/mL, respectively. There was no difference in the median C max of rifampicin among those who had hepatotoxicity and those who did not ( P  =   0.322). There was no difference in the isoniazid median C max among those who had peripheral neuropathy 2.34 (1.52-3.23) μg/mL and those who did not 2.21 (1.45-3.11) μg/mL ( P  =   0.49). There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.

  4. Modulation of HCV Replication After Combination Antiretroviral Therapy in HCV/HIV Coinfected Patients

    PubMed Central

    Sherman, Kenneth E.; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T.; Rouster, Susan D.; Castro, Mario; Feinberg, Judith; Sterling, Richard K.; Goodman, Zachary; Aronow, Bruce J.; Perelson, Alan S.

    2015-01-01

    The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients coinfected with human immunodeficiency virus (HIV). Coinfection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV coinfected patients into a cART initiation trial, and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in HCV flare and alanine aminotransferase (ALT) increase (2× or more increase from baseline) in a subset of treated patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in patients who underwent successful cART, particularly with respect to downregulation of genes with known antiviral roles. Our findings suggest that the effective suppression of HIV by cART initiates a cascade of early and late events in treated patients with HCV. Early events involving downregulation of interferon-stimulated genes may lead to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declines to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV coinfection. PMID:25101888

  5. Granzyme B as a diagnostic marker of tuberculosis in patients with and without HIV coinfection.

    PubMed

    Sarkar, Pronoti; Mitra, Soumik; Pant, Priyannk; Kotwal, Aarti; Kakati, Barnali; Masih, Victor; Sindhwani, Girish; Biswas, Debasis

    2016-05-01

    Immunodiagnostic tests for tuberculosis (TB) are based on the estimation of interferon γ (IFN-γ) or IFN-γ-secreting CD4(+) T cells following ex vivo stimulation with ESAT6 and CFP-10. Sensitivity of these tests is likely to be compromised in CD4(+) T-cell-depleted situations, like HIV-TB coinfection. CD4(+) and CD8(+) T cells, isolated from 3 groups, viz., HIV-negative patients with active TB, HIV-TB coinfected patients, and healthy household contacts (HHCs) were cocultivated with autologous dendritic cells, and the cytokine response to rESAT6 stimulation was compared between groups in supernatants. While CD4(+) T-cell stimulation yielded significantly elevated levels of IFN-γ and interleukin 4 in HIV-negative TB patients, compared to HHCs, the levels of both these cytokines were nondiscriminatory between HIV-positive TB patients and HHCs. However, CD8(+) T-cell stimulation yielded significantly elevated granzyme B titers in both groups of patients, irrespective of HIV coinfection status. Hence, contrary to IFN-γ, granzyme B might be a useful diagnostic marker for Mycobacterium tuberculosis infection particularly in HIV coinfected patients.

  6. Serological diagnosis of paracoccidioidomycosis in HIV-coinfected patients.

    PubMed

    Bellissimo-Rodrigues, Fernando; Vitali, Lucia Helena; Martinez, Roberto

    2010-11-01

    Paracoccidioidomycosis should be differentiated from other opportunistic diseases in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients who live in Latin America. Laboratory investigation can begin with serological tests, which are rapid and efficient. In the present study, double immunodiffusion (DID), counterimmunoelectrophoresis (CIEP) and an enzyme linked immunosorbent assay (ELISA) tests were assessed for the detection of anti-Paracoccidioides brasiliensis antibodies in 40 patients coinfected with HIV. The results were compared to those obtained for 75 non-HIV-infected patients with endemic paracoccidioidomycosis. Anti-P. brasiliensis antibodies were detected in 65% (DID), 79% (CIEP) and 95% (ELISA) of the patients with HIV/AIDS, significantly lower rates than those detected in cases of endemic paracoccidioidomycosis, which were 89%, 99% and 100%, respectively. The reactive sera of HIV-infected patients also showed lower anti-P. brasiliensis antibody titres than those of non-HIV-infected patients. Despite the lower intensity of the specific humoral response, serological tests are useful for the diagnosis of opportunistic paracoccidioidomycosis in the HIV/AIDS population. We suggest optimization of the laboratory diagnosis by combining the ELISA test with CIEP or DID.

  7. Intrahepatic CD4+ cell depletion in hepatitis C virus/HIV-coinfected patients.

    PubMed

    Canchis, P Wilfredo; Yee, Herman T; Fiel, M Isabel; Dieterich, Douglas T; Liu, Ruei-Che; Chiriboga, Luis; Jacobson, Ira M; Edlin, Brian R; Talal, Andrew H

    2004-09-01

    Coinfection with HIV and hepatitis C virus (HCV)-specific immune responses, increases hepatic inflammation, accelerates hepatic fibrosis, and is associated with deceased treatment responses. We quantified intrahepatic lymphocyte and hepatocyte phenotypes in HCV-infected patients with (n = 38) and without (n = 41) HIV infection. A single pathologist counted positive cells in 5 portal and 5 lobular areas. Coinfected patients had 6.81 +/- 1.9 fewer CD4 cells per portal field (10.58 +/- 1.12 vs. 4.97 +/- 1.09 cells/high-power field [HPF]; P < 0.001) and 0.48 +/- 0.15 more apoptotic lymphocytes per lobular field (0.16 +/- 0.06 vs. 0.64 +/- 0.15 cell/HPF; P = 0.002) than monoinfected patients. The number of portal CD4 cells was not associated with the peripheral CD4 cell number. Portal and lobular CD8 cells did not differ between the 2 groups. Portal proliferative hepatocytes were increased in coinfected patients with HIV RNA levels of >400 copies/mL (1.13 +/- 0.32 cells/HPF; P = 0.01) compared with those with undetectable HIV RNA (0.46 +/- 0.09 cell/HPF) and monoinfected patients (0.45 +/- 0.08 cell/HPF). In conclusion, HIV coinfection is associated with fewer portal CD4 cells and increased lobular lymphocyte apoptosis that may impact on the natural history of HCV infection.

  8. Liver Enzyme Alterations in HCV-Monoinfected and HCV/HIV-Coinfected Patients

    PubMed Central

    Langohr, Klaus; Sanvisens, Arantza; Fuster, Daniel; Tor, Jordi; Serra, Isabel; Rey-Joly, Celestino; Rivas, Inmaculada; Muga, Roberto

    2008-01-01

    Hepatitis C virus (HCV) is the most common blood-borne infection in developed countries and co-infection with the Human Immunodeficiency Virus (HIV) is frequent in individuals with history of injecting drug use (IDU). We aimed to analyze liver transaminases in HCV monoinfected and HCV/HIV co-infected patients to assess the effect of HIV infection on liver enzyme elevations. We studied 429 current IDUs admitted to substance abuse treatment (82.5% males). Serum samples for liver tests, HIV infection and viral hepatitis serologies were obtained at admission. Results: Median age was 30 years (IQR:27-34), median duration of IDU was 10 years (IQR:5-14), 52% of patients were HCV/HIV co-infected, 40.8% were HCV monoinfected, and 7.2% were HCV and HIV- seronegatives. Elevated AST was associated with male gender and lower CD8+ cell count in the HCV monoinfected patients, and with age and lower cholesterol in the HCV/HIV coinfected subjects. ALT elevation was associated with younger age, higher body mass index and male gender in the monoinfected patients, and with higher CD4+ cell counts and lower cholesterol in the co-infected group. Male sex was strongly associated with elevated ALT and AST transaminase in the monoinfected but not in dual-infected subjects. These data suggest that the effect of gender on liver enzymes may be lost in patients with HIV infection. The overall differences observed between groups regarding liver enzyme elevations are of clinical relevance in the management of IDUs with chronic hepatitis C. PMID:19274066

  9. Improving HCV cure rates in HIV-coinfected patients - a real-world perspective.

    PubMed

    Lakshmi, Seetha; Alcaide, Maria; Palacio, Ana M; Shaikhomer, Mohammed; Alexander, Abigail L; Gill-Wiehl, Genevieve; Pandey, Aman; Patel, Kunal; Jayaweera, Dushyantha; Del Pilar Hernandez, Maria

    2016-05-01

    To study rates and predictors of hepatitis C virus (HCV) cure among human immunodeficiency virus (HIV)/HCV-coinfected patients, and then to evaluate the effect of attendance at clinic visits on HCV cure. Retrospective cohort study of adult HIV/HCV-coinfected patients who initiated and completed treatment for HCV with direct-acting antivirals (DAAs) between January 1, 2014, and June 30, 2015. Eighty-four participants reported completing treatment. The median age was 58 years (interquartile ratio, 50-66); 88% were male and 50% were black. One-third were cirrhotic and half were HCV-treatment-experienced. The most commonly used regimen was sofosbuvir/ledipasvir (40%) followed by simeprevir/sofosbuvir (30%). Cure was achieved in 83.3%, 11.9% relapsed, and 2.3% experienced virological breakthrough. Two patients (2.3%) did not complete treatment based on pill counts and follow-up visit documentation. In multivariable analysis, cure was associated with attendance at follow-up clinic visits (odds ratio [OR], 9.0; 95% CI, 2.91-163) and with use of an integrase-based HIV regimen versus other non-integrase regimens, such as non-nucleoside analogues or protease inhibitors (OR, 6.22; 95% CI 1.81-141). Age, race, genotype, presence of cirrhosis, prior HCV treatment, HCV regimen, and pre-treatment CD4 counts were not associated with cure. Real-world HCV cure rates with DAAs in HCV/HIV coinfection are lower than those seen in clinical trials. Cure is associated with attendance at follow-up clinic visits and with use of an integrase-based HIV regimen. Future studies should evaluate best antiretroviral regimens, predictors of attendance at follow-up visits, impact of different monitoring protocols on medication adherence, and interventions to ensure adequate models of HIV/HCV care.

  10. Successful Treatment of Hepatitis C with Simeprevir, Sofosbuvir, and Ribavirin in an HIV Coinfected Liver Transplant Patient with Advanced Chronic Kidney Disease.

    PubMed

    Maruyama, Anna; Hussaini, Trana; Partovi, Nilufar; Erb, Siegfried R; Azalgara, Vladimir Marquez; Zalunardo, Nadia; Pick, Neora; Hull, Mark; Yoshida, Eric M

    2016-01-01

    Although major advances have occurred in treating patients with hepatitis C virus (HCV) with the development of new direct-acting antivirals (DAAs), treatment of liver transplant recipients with HCV, human immunodeficiency virus (HIV) coinfection, and renal disease is challenging due to the lack of efficacy and safety data in this population. We report a case of successful HCV therapy in a postliver transplant HIV coinfected patient, with stage 4 chronic kidney disease, using an all-oral regimen of simeprevir, sofosbuvir, and ribavirin. The 51-year-old male achieved SVR24, and no specific HIV-related or transplant-related adverse events were documented during the treatment period. The new DAAs show promise for HIV coinfected patients and those with severe to end-stage renal disease (ESRD); however, robust clinical trials or large cohort studies will need to be conducted to confirm the efficacy and safety of these newer agents in this setting.

  11. Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection.

    PubMed

    Sulkowski, Mark S; Naggie, Susanna; Lalezari, Jacob; Fessel, Walford Jeffrey; Mounzer, Karam; Shuhart, Margaret; Luetkemeyer, Anne F; Asmuth, David; Gaggar, Anuj; Ni, Liyun; Svarovskaia, Evguenia; Brainard, Diana M; Symonds, William T; Subramanian, G Mani; McHutchison, John G; Rodriguez-Torres, Maribel; Dieterich, Douglas

    Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon. To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment. Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants. Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks. The primary study outcome was the proportion of patients with SVR (serum HCV <25 copies/mL) 12 weeks (SVR12) after cessation of HCV therapy. Among treatment-naive participants, 87 patients (76%) of 114 (95% CI, 67%-84%) with genotype 1, 23 patients (88%) of 26 with genotype 2 (95% CI, 70%-985), and 28 patients (67%) of 42 with genotype 3 (95% CI, 51%-80%) achieved SVR12. Among treatment-experienced participants, 22 patients (92%) of 24 with genotype 2 (95% CI, 73%-99%) and 16 patients (94%) of 17 (95% CI, 71%-100%) achieved SVR12. The most common adverse events were fatigue, insomnia

  12. Evolution and function of the HCV NS3 protease in patients with acute hepatitis C and HIV coinfection.

    PubMed

    Dietz, Julia; Lutz, Thomas; Knecht, Gaby; Gute, Peter; Berkowski, Caterina; Lange, Christian Markus; Khaykin, Pavel; Stephan, Christoph; Brodt, Hans-Reinhard; Herrmann, Eva; Zeuzem, Stefan; Sarrazin, Christoph

    2015-11-01

    Little is known about the importance of the hepatitis C virus (HCV) NS3 protease in acute hepatitis C. In this prospective study, 82 consecutive patients with acute hepatitis C and human immunodeficiency virus (HIV) coinfection were enrolled. Individuals were infected with highly related HCV strains and the baseline NS3 quasispecies diversity and complexity was higher compared to a chronic hepatitis C control group (P<0.0001). Both parameters were comparable in patients with spontaneous clearance (n=6) versus treatment-induced SVR (n=5) or development of chronic hepatitis C (n=9). Longitudinal NS3 quasispecies kinetics showed a trend to a decreasing diversity and complexity (P<0.05) within 4 weeks in patients with spontaneous clearance compared to the other groups. The innate immune signalling protein CARDIF was cleaved to a similar extent independent of the outcome. Together with a more pronounced viral load decline (P<0.05), an early decreasing NS3 quasispecies evolution indicates spontaneous clearance of acute hepatitis C. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Liver Damage in Patients with HCV/HIV Coinfection Is Linked to HIV-Related Oxidative Stress

    PubMed Central

    Huang, Xiangbo; Liang, Hua; Fan, Xueying; Zhu, Liyan; Shen, Tao

    2016-01-01

    HIV infection aggravates the progression of liver damage in HCV-coinfected patients, with the underlying pathogenesis being multifactorial. Although high level of oxidative stress has been observed frequently in patients infected with HIV or HCV, the status of oxidative stress in HIV/HCV coinfection and its contribution to HCV liver damage have not been determined. This study involved 363 HBsAg-negative, anti-HCV-positive former blood donors recruited from a village in central China in July 2005; of these, 140 were positive for HIV. Of these 363 subjects, 282 were successfully followed up through July 2009. HIV/HCV-coinfected subjects had higher rates of end-stage liver disease-related death than those monoinfected with HCV. Liver ultrasound manifestations were poor in HIV-positive than in HIV-negative individuals, in both chronic HCV carriers and those with resolved HCV. Serum concentrations of total glutathione (tGSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), GSSG, and reduced GSH were higher in HIV-positive than HIV-negative subjects. GSSG concentrations were higher in HIV-infected subjects with abnormal ALT/AST levels than in those with normal ALT/AST levels and were associated with poorer liver ultrasound manifestations. These finding indicated that HIV infection accelerated HCV-associated liver damage in HIV/HCV-coinfected individuals. Increased oxidative stress, induced primarily by HIV coinfection, may contribute to aggravated liver damage. PMID:26881041

  14. Diagnostic accuracy of the genotype MTBDRsl assay for rapid diagnosis of extensively drug-resistant tuberculosis in HIV-coinfected patients.

    PubMed

    Kontsevaya, Irina; Ignatyeva, Olga; Nikolayevskyy, Vladyslav; Balabanova, Yanina; Kovalyov, Alexander; Kritsky, Andrey; Matskevich, Olesya; Drobniewski, Francis

    2013-01-01

    The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of Mycobacterium tuberculosis multidrug resistance (MDR) and extensive drug resistance (XDR), especially in HIV-coinfected patients. Rapid and reliable diagnosis for detection of resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the GenoType MTBDRsl (Hain Lifescience GmbH, Nehren, Germany) assay on smear-positive sputum specimens obtained from 90 HIV-infected MDR TB patients from Russia. Test interpretability was over 98%. Specificity was over 86% for all drugs, while sensitivity varied, being the highest (71.4%) for capreomycin and lowest (9.4%) for kanamycin, probably due to the presence of mutations in the eis gene. The sensitivity of detection of XDR TB was 13.6%, increasing to 42.9% if kanamycin (not commonly used in Western Europe) was excluded. The assay is a highly specific screening tool for XDR detection in direct specimens from HIV-coinfected TB patients but cannot be used to rule out XDR TB.

  15. Treatment Options for Visceral Leishmaniasis and HIV Coinfection.

    PubMed

    Monge-Maillo, Begoña; López-Vélez, Rogelio

    2016-01-01

    Leishmania and HIV coinfection is a major health problem in more than 35 countries worldwide. The impaired immune function of visceral leishmaniasis/HIV-coinfected patients may: (i) favor the reactivation of latent Leishmania infection; (ii) induce a more severe presentation of visceral leishmaniasis; (iii) cause a poorer therapeutic response; and (iv) increase the risk of relapse after treatment. One of the major challenges in the management of visceral leishmaniasis/HIV coinfection is developing an effective drug therapy that not only resolves the first episode of visceral leishmaniasis but also prevents relapse. However, scarce evidence and data are available on the optimal therapy for visceral leishmaniasis/HIV coinfection. In our study we reviewed the efficacy of several drugs currently employed for visceral leishmaniasis in HIV patients and current knowledge of secondary prophylaxis. Additionally, we reviewed a set of ongoing clinical trials that are being performed to evaluate the efficacy of new therapeutic regimens for visceral leishmaniasis in patients with and without HIV. Finally, other therapeutic strategies based on immunotherapy, vaccination, or screening for latent leishmaniasis infection in HIV patients are reviewed. Apart from being potentially useful in clinical practice, the results obtained in our study highlight the need for further research on the management of visceral leishmaniasis/HIV coinfection.

  16. Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America.

    PubMed

    Efsen, Anne Marie W; Schultze, Anna; Post, Frank A; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert F; Losso, Marcelo H; Toibaro, Javier; Skrahin, Aliaksandr; Miro, Jose M; Caylà, Joan A; Girardi, Enrico; Bruyand, Mathias; Obel, Niels; Podlekareva, Daria N; Lundgren, Jens D; Mocroft, Amanda; Kirk, Ole

    2015-01-01

    Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00-4.09), prior anti-TB treatment (3.42 (1.88-6.22)), and living in EE (7.19 (3.28-15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90-96% in other regions (p<0.0001). In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART.

  17. Major Challenges in Clinical Management of TB/HIV Coinfected Patients in Eastern Europe Compared with Western Europe and Latin America

    PubMed Central

    Efsen, Anne Marie W.; Schultze, Anna; Post, Frank A.; Panteleev, Alexander; Furrer, Hansjakob; Miller, Robert F.; Losso, Marcelo H.; Toibaro, Javier; Skrahin, Aliaksandr; Miro, Jose M.; Caylà, Joan A.; Girardi, Enrico; Bruyand, Mathias; Obel, Niels; Podlekareva, Daria N.; Lundgren, Jens D.; Mocroft, Amanda; Kirk, Ole

    2015-01-01

    Objectives Rates of TB/HIV coinfection and multi-drug resistant (MDR)-TB are increasing in Eastern Europe (EE). We aimed to study clinical characteristics, factors associated with MDR-TB and predicted activity of empiric anti-TB treatment at time of TB diagnosis among TB/HIV coinfected patients in EE, Western Europe (WE) and Latin America (LA). Design and Methods Between January 1, 2011, and December 31, 2013, 1413 TB/HIV patients (62 clinics in 19 countries in EE, WE, Southern Europe (SE), and LA) were enrolled. Results Significant differences were observed between EE (N = 844), WE (N = 152), SE (N = 164), and LA (N = 253) in the proportion of patients with a definite TB diagnosis (47%, 71%, 72% and 40%, p<0.0001), MDR-TB (40%, 5%, 3% and 15%, p<0.0001), and use of combination antiretroviral therapy (cART) (17%, 40%, 44% and 35%, p<0.0001). Injecting drug use (adjusted OR (aOR) = 2.03 (95% CI 1.00–4.09), prior anti-TB treatment (3.42 (1.88–6.22)), and living in EE (7.19 (3.28–15.78)) were associated with MDR-TB. Among 585 patients with drug susceptibility test (DST) results, the empiric (i.e. without knowledge of the DST results) anti-TB treatment included ≥3 active drugs in 66% of participants in EE compared with 90–96% in other regions (p<0.0001). Conclusions In EE, TB/HIV patients were less likely to receive a definite TB diagnosis, more likely to house MDR-TB and commonly received empiric anti-TB treatment with reduced activity. Improved management of TB/HIV patients in EE requires better access to TB diagnostics including DSTs, empiric anti-TB therapy directed at both susceptible and MDR-TB, and more widespread use of cART. PMID:26716686

  18. HIV-coinfected patients respond worse to direct-acting antiviral-based therapy against chronic hepatitis C in real life than HCV-monoinfected individuals: a prospective cohort study.

    PubMed

    Neukam, Karin; Morano-Amado, Luis E; Rivero-Juárez, Antonio; Mancebo, María; Granados, Rafael; Téllez, Francisco; Collado, Antonio; Ríos, María J; de Los Santos-Gil, Ignacio; Reus-Bañuls, Sergio; Vera-Méndez, Francisco; Geijo-Martínez, Paloma; Montero-Alonso, Marta; Suárez-Santamaría, Marta; Pineda, Juan A

    2017-05-01

    HIV/HCV-coinfected patients and hepatitis C virus (HCV) monoinfected subjects are thought to respond equally to direct-acting antiviral (DAA)-based therapy despite the lack of data derived from clinical trials. This study is aimed to evaluate the impact of HIV coinfection on the response to DAA-based treatment against HCV infection in the clinical practice. In a prospective multicohort study, patients who initiated DAA-based therapy at the Infectious Disease Units of 33 hospitals throughout Spain were included. The primary efficacy outcome variables were the achievement of sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12). A total of 908 individuals had reached the SVR12 evaluation time-point, 426 (46.9%) were HIV/HCV-coinfected, and 472 (52%) received interferon (IFN)-free therapy. In an intention-to-treat analysis, SVR12 rates in subjects with and without HIV-coinfection were 55.3% (94/170 patients) versus 67.3% (179/266 subjects; p = 0.012) for IFN-based treatment and 86.3% (221/256 subjects) versus 94.9% (205/216 patients, p = 0.002) for IFN-free regimens. Relapse after end-of-treatment response to IFN-free therapy was observed in 3/208 (1.4%) HCV-monoinfected subjects and 10/231 (4.4%) HIV/HCV-coinfected individuals (p = 0.075). In a multivariate analysis adjusted for age, sex, transmission route, body-mass index, HCV genotype, and cirrhosis, the absence of HIV-coinfection (adjusted odds ratio: 3.367; 95% confidence interval: 1.15-9.854; p = 0.027) was independently associated with SVR12 to IFN-free therapy. HIV-coinfection is associated with worse response to DAA-based therapy against HCV infection. In patients receiving IFN-free therapy, this fact seems to be mainly driven by a higher rate of relapses among HIV-coinfected subjects.

  19. Breaking down the barriers to hepatitis C virus (HCV) treatment among individuals with HCV/HIV coinfection: action required at the system, provider, and patient levels.

    PubMed

    Grebely, Jason; Oser, Megan; Taylor, Lynn E; Dore, Gregory J

    2013-03-01

    The majority of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection occurs among persons who inject drugs. Rapid improvements in responses to HCV therapy have been observed, but liver-related morbidity rates remain high, given notoriously low uptake of HCV treatment. Advances in HCV therapy will have a limited impact on the burden of HCV-related disease at the population-level unless barriers to HCV education, screening, evaluation, and treatment are addressed and treatment uptake increases. This review will outline barriers to HCV care in HCV/HIV coinfection, with a particular emphasis on persons who inject drugs, proposing strategies to enhance HCV treatment uptake and outcomes.

  20. Influence of IL28B polymorphisms on response to a lower-than-standard dose peg-IFN-α 2a for genotype 3 chronic hepatitis C in HIV-coinfected patients.

    PubMed

    López-Cortés, Luis F; Ruiz-Valderas, Rosa; Jimenez-Jimenez, Luis; González-Escribano, María F; Torres-Cornejo, Almudena; Mata, Rosario; Rivero, Antonio; Pineda, Juan A; Marquez-Solero, Manuel; Viciana, Pompeyo

    2012-01-01

    Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients. Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype. Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses. ClinicalTrials.gov NCT00553930.

  1. Influence of IL28B Polymorphisms on Response to a Lower-Than-Standard Dose peg-IFN-α 2a for Genotype 3 Chronic Hepatitis C in HIV-Coinfected Patients

    PubMed Central

    López-Cortés, Luis F.; Ruiz-Valderas, Rosa; Jimenez-Jimenez, Luis; González-Escribano, María F.; Torres-Cornejo, Almudena; Mata, Rosario; Rivero, Antonio; Pineda, Juan A.; Marquez-Solero, Manuel; Viciana, Pompeyo

    2012-01-01

    Background Data on which to base definitive recommendations on the doses and duration of therapy for genotype 3 HCV/HIV-coinfected patients are scarce. We evaluated the efficacy of a lower peginterferon-α 2a dose and a shorter duration of therapy than the current standard of care in genotype 3 HCV/HIV-coinfected patients. Methods and Findings Pilot, open-label, single arm clinical trial which involved 58 Caucasian HCV/HIV-coinfected patients who received weekly 135 µg peginterferon-α 2a plus ribavirin 400 mg twice daily during 20 weeks after attaining undetectable viremia. The relationships between baseline patient-related variables, including IL28B genotype, plasma HCV-RNA, ribavirin dose/kg, peginterferon-α 2a and ribavirin levels with virological responses were analyzed. Only 4 patients showed lack of response and 5 patients dropped out due to adverse events related to the study medication. Overall, sustained virologic response (SVR) rates were 58.3% by intention-to-treat and 71.4% by per protocol analysis, respectively. Among patients with rapid virologic response (RVR), SVR and relapses rates were 92.6% and 7.4%, respectively. No relationships were observed between viral responses and ribavirin dose/kg, peginterferon-α 2a concentrations, ribavirin levels or rs129679860 genotype. Conclusions Weekly 135 µg pegIFN-α 2a could be as effective as the standard 180 µg dose, with a very low incidence of severe adverse events. A 24-week treatment duration appears to be appropriate in patients achieving RVR, but extending treatment up to just 20 weeks beyond negativization of viremia is associated with a high relapse rate in those patients not achieving RVR. There was no influence of IL28B genotype on the virological responses. Trial Registration: ClinicalTrials.gov NCT00553930 PMID:22235243

  2. Visceral Leishmaniasis and HIV Coinfection in the Mediterranean Region

    PubMed Central

    Monge-Maillo, Begoña; Norman, Francesca F.; Cruz, Israel; Alvar, Jorge; López-Vélez, Rogelio

    2014-01-01

    Visceral leishmaniasis is hypoendemic in Mediterranean countries, where it is caused by the flagellate protozoan Leishmania infantum. VL cases in this area account for 5%–6% of the global burden. Cases of Leishmania/HIV coinfection have been reported in the Mediterranean region, mainly in France, Italy, Portugal, and Spain. Since highly active antiretroviral therapy was introduced in 1997, a marked decrease in the number of coinfected cases in this region has been reported. The development of new diagnostic methods to accurately identify level of parasitemia and the risk of relapse is one of the main challenges in improving the treatment of coinfected patients. Clinical trials in the Mediterranean region are needed to determine the most adequate therapeutic options for Leishmania/HIV patients as well as the indications and regimes for secondary prophylaxis. This article reviews the epidemiological, diagnostic, clinical, and therapeutic aspects of Leishmania/HIV coinfection in the Mediterranean region. PMID:25144380

  3. Visceral Leishmaniasis and HIV coinfection in East Africa.

    PubMed

    Diro, Ermias; Lynen, Lutgarde; Ritmeijer, Koert; Boelaert, Marleen; Hailu, Asrat; van Griensven, Johan

    2014-06-01

    Visceral Leishmaniasis (VL) is an important protozoan opportunistic disease in HIV patients in endemic areas. East Africa is second to the Indian subcontinent in the global VL caseload and first in VL-HIV coinfection rate. Because of the alteration in the disease course, the diagnostic challenges, and the poor treatment responses, VL with HIV coinfection has become a very serious challenge in East Africa today. Field experience with the use of liposomal amphotericin B in combination with miltefosine, followed by secondary prophylaxis and antiretroviral drugs, looks promising. However, this needs to be confirmed through clinical trials. Better diagnostic and follow-up methods for relapse and prediction of relapse should also be looked for. Basic research to understand the immunological interaction of the two infections may ultimately help to improve the management of the coinfection.

  4. Visceral leishmaniasis and HIV coinfection in Latin America.

    PubMed

    Lindoso, José Angelo; Cota, Gláucia Fernandes; da Cruz, Alda Maria; Goto, Hiro; Maia-Elkhoury, Ana Nilce Silveira; Romero, Gustavo Adolfo Sierra; de Sousa-Gomes, Márcia Leite; Santos-Oliveira, Joanna Reis; Rabello, Ana

    2014-09-01

    Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for

  5. Visceral Leishmaniasis and HIV Coinfection in Latin America

    PubMed Central

    Lindoso, José Angelo; Cota, Gláucia Fernandes; da Cruz, Alda Maria; Goto, Hiro; Maia-Elkhoury, Ana Nilce Silveira; Romero, Gustavo Adolfo Sierra; de Sousa-Gomes, Márcia Leite; Santos-Oliveira, Joanna Reis; Rabello, Ana

    2014-01-01

    Visceral leishmaniasis (VL) is an endemic zoonotic disease in Latin America caused by Leishmania (Leishmania) infantum, which is transmitted by sand flies from the genus Lutzomyia. VL occurs in 12 countries of Latin America, with 96% of cases reported in Brazil. Recently, an increase in VL, primarily affecting children and young adults, has been observed in urban areas of Latin America. The area in which this spread of VL is occurring overlaps regions with individuals living with HIV, the number of whom is estimated to be 1.4 million people by the World Health Organization. This overlap is suggested to be a leading cause of the increased number of reported VL-HIV coinfections. The clinical progression of HIV and L. infantum infections are both highly dependent on the specific immune response of an individual. Furthermore, the impact on the immune system caused by either pathogen and by VL-HIV coinfection can contribute to an accelerated progression of the diseases. Clinical presentation of VL in HIV positive patients is similar to patients without HIV, with symptoms characterized by fever, splenomegaly, and hepatomegaly, but diarrhea appears to be more common in coinfected patients. In addition, VL relapses are higher in coinfected patients, affecting 10% to 56.5% of cases and with a lethality ranging from 8.7% to 23.5% in Latin America, depending on the study. With regards to the diagnosis of VL, parasitological tests of bone marrow aspirates have proven to be the most sensitive test in HIV-infected patients. Serologic tests have demonstrated a variable sensitivity according to the method and antigens used, with the standard tests used for diagnosing VL in Latin America displaying lower sensitivity. For this review, few articles were identified that related to VL-HIV coinfections and originated from Latin America, highlighting the need for improving research within the regions most greatly affected. We strongly support the formation of a Latin American network for

  6. The Need to Reevaluate Nonresponding Ergonomic Patients

    NASA Technical Reports Server (NTRS)

    Scarpa, Philip J.; Field, Steven A.

    1999-01-01

    The Kennedy Space Center (KSC) Environmental Health (EH) contractor performs ergonomic evaluations under its Ergonomic Program. Any KSC employee may request one or the reviewing physician may request one for a patient during a visit to an onsite medical facility. As part of the ergonomic evaluation, recommendations are given to the patient to help reduce any ergonomic problems they experience. The recommendations, if implemented, are successful in the majority of KSC patients; however, a group of patients do not seem to improve. Those who don't improve may be identified by reevaluations, which are performed to implement maximum resolution of ergonomic problems.

  7. The Need to Reevaluate Nonresponding Ergonomic Patients

    NASA Technical Reports Server (NTRS)

    Scarpa, Philip J.; Field, Steven A.

    1999-01-01

    The Kennedy Space Center (KSC) Environmental Health (EH) contractor performs ergonomic evaluations under its Ergonomic Program. Any KSC employee may request one or the reviewing physician may request one for a patient during a visit to an onsite medical facility. As part of the ergonomic evaluation, recommendations are given to the patient to help reduce any ergonomic problems they experience. The recommendations, if implemented, are successful in the majority of KSC patients; however, a group of patients do not seem to improve. Those who don't improve may be identified by reevaluations, which are performed to implement maximum resolution of ergonomic problems.

  8. Leishmaniasis-HIV coinfection: current challenges.

    PubMed

    Lindoso, José Angelo Lauletta; Cunha, Mirella Alves; Queiroz, Igor Thiago; Moreira, Carlos Henrique Valente

    2016-01-01

    Leishmaniasis - human immunodeficiency virus (HIV) coinfection can manifest itself as tegumentary or visceral leishmaniasis. Almost 35 countries have reported autochthonous coinfections. Visceral leishmaniasis is more frequently described. However, usual and unusual manifestations of tegumentary leishmaniasis have been reported mainly in the Americas, but the real prevalence of Leishmania infection in HIV-infected patients is not clear. Regarding the clinical manifestations, there are some reports showing unusual manifestations in visceral leishmaniasis and tegumentary leishmaniasis in HIV-infected patients; yet, the usual manifestations are more frequent. Leishmaniasis diagnosis relies on clinical methods, but serological tests are used to diagnose visceral leishmaniasis despite them having a low sensitivity to tegumentary leishmaniasis. The search for the parasite is used to diagnose both visceral leishmaniasis and tegumentary leishmaniasis. Nevertheless, in HIV-infected patients, the sensitivity of serology is very low. Drugs available to treat leishmaniasis are more restricted and cause severe side effects. Furthermore, in HIV-infected patients, these side effects are more prominent and relapses and lethality are more recurrent. In this article, we discuss the current challenges of tegumentary leishmaniasis and visceral leishmaniasis-HIV infection, focusing mainly on the clinical manifestations, diagnosis, and treatment of leishmaniasis.

  9. Leishmaniasis–HIV coinfection: current challenges

    PubMed Central

    Lindoso, José Angelo Lauletta; Cunha, Mirella Alves; Queiroz, Igor Thiago; Moreira, Carlos Henrique Valente

    2016-01-01

    Leishmaniasis – human immunodeficiency virus (HIV) coinfection can manifest itself as tegumentary or visceral leishmaniasis. Almost 35 countries have reported autochthonous coinfections. Visceral leishmaniasis is more frequently described. However, usual and unusual manifestations of tegumentary leishmaniasis have been reported mainly in the Americas, but the real prevalence of Leishmania infection in HIV-infected patients is not clear. Regarding the clinical manifestations, there are some reports showing unusual manifestations in visceral leishmaniasis and tegumentary leishmaniasis in HIV-infected patients; yet, the usual manifestations are more frequent. Leishmaniasis diagnosis relies on clinical methods, but serological tests are used to diagnose visceral leishmaniasis despite them having a low sensitivity to tegumentary leishmaniasis. The search for the parasite is used to diagnose both visceral leishmaniasis and tegumentary leishmaniasis. Nevertheless, in HIV-infected patients, the sensitivity of serology is very low. Drugs available to treat leishmaniasis are more restricted and cause severe side effects. Furthermore, in HIV-infected patients, these side effects are more prominent and relapses and lethality are more recurrent. In this article, we discuss the current challenges of tegumentary leishmaniasis and visceral leishmaniasis–HIV infection, focusing mainly on the clinical manifestations, diagnosis, and treatment of leishmaniasis. PMID:27785103

  10. Chronic hepatitis B increases mortality and complexity among HIV-coinfected patients in South Africa: a cohort study.

    PubMed

    Velen, K; Charalambous, S; Innes, C; Churchyard, G J; Hoffmann, C J

    2016-10-01

    To assess the effect of chronic hepatitis B on survival and clinical complexity among people living with HIV following antiretroviral therapy (ART) initiation. We evaluated mortality and single-drug substitutions up to 3 years from ART initiation (median follow-up 2.75 years; interquartile range 2-3 years) among patients with and without chronic hepatitis B (CHB) enrolled in a workplace HIV care programme in South Africa. Mortality was increased for CHB patients with hepatitis B virus (HBV) DNA levels > 10 000 copies/mL (adjusted hazard ratio 3.1; 95% confidence interval 1.2-8.0) compared with non-CHB patients. We did not observe a similar difference between non-CHB patients and those with CHB and HBV DNA < 10 000 copies/mL (adjusted hazard ratio 0.70; 95% confidence interval 0.2-2.3). Single-drug substitutions occurred more frequently among coinfected patients regardless of HBV DNA level. Our findings suggest that CHB may increase mortality and complicate ART management. © 2016 British HIV Association.

  11. Pharmacokinetics of Rifampin and Isoniazid in Tuberculosis-HIV-Coinfected Patients Receiving Nevirapine- or Efavirenz-Based Antiretroviral Treatment

    PubMed Central

    Bhatt, N. B.; Barau, C.; Amin, A.; Baudin, E.; Meggi, B.; Silva, C.; Furlan, V.; Grinsztejn, B.; Barrail-Tran, A.; Bonnet, M.

    2014-01-01

    This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4+ T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of

  12. Pharmacokinetics of rifampin and isoniazid in tuberculosis-HIV-coinfected patients receiving nevirapine- or efavirenz-based antiretroviral treatment.

    PubMed

    Bhatt, N B; Barau, C; Amin, A; Baudin, E; Meggi, B; Silva, C; Furlan, V; Grinsztejn, B; Barrail-Tran, A; Bonnet, M; Taburet, A M

    2014-06-01

    This is a substudy of the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS) Comparison of Nevirapine and Efavirenz for the Treatment of HIV-TB Co-infected Patients (ANRS 12146-CARINEMO) trial, which assessed the pharmacokinetics of rifampin or isoniazid with or without the coadministration of nonnucleoside reverse transcriptase inhibitor-based HIV antiretroviral therapy in HIV-tuberculosis-coinfected patients in Mozambique. Thirty-eight patients on antituberculosis therapy based on rifampin and isoniazid participated in the substudy (57.9% males; median age, 33 years; median weight, 51.9 kg; median CD4(+) T cell count, 104 cells/μl; median HIV-1 RNA load, 5.5 log copies/ml). The daily doses of rifampin and isoniazid were 10 and 5 mg/kg of body weight, respectively. Twenty-one patients received 200 mg of nevirapine twice a day (b.i.d.), and 17 patients received 600 mg of efavirenz once a day (q.d.) in combination with lamivudine and stavudine from day 1 until the end of the study. Blood samples were collected at regular time-dosing intervals after morning administration of a fixed-dose combination of rifampin and isoniazid. When rifampin was administered alone, the median maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve (AUC) at steady state were 6.59 mg/liter (range, 2.70 to 14.07 mg/liter) and 27.69 mg · h/liter (range, 11.41 to 109.75 mg · h/liter), respectively. Concentrations remained unchanged when rifampin was coadministered with nevirapine or efavirenz. When isoniazid was administered alone, the median isoniazid Cmax and AUC at steady state were 5.08 mg/liter (range, 1.26 to 11.51 mg/liter) and 20.92 mg · h/liter (range, 7.73 to 56.95 mg · h/liter), respectively. Concentrations remained unchanged when isoniazid was coadministered with nevirapine; however, a 29% decrease in the isoniazid AUC was observed when isoniazid was combined with efavirenz. The pharmacokinetic parameters of

  13. Deconvoluting the Composition of Low-Frequency Hepatitis C Viral Quasispecies: Comparison of Genotypes and NS3 Resistance-Associated Variants between HCV/HIV Coinfected Hemophiliacs and HCV Monoinfected Patients in Japan

    PubMed Central

    Ogishi, Masato; Yotsuyanagi, Hiroshi; Tsutsumi, Takeya; Gatanaga, Hiroyuki; Ode, Hirotaka; Sugiura, Wataru; Moriya, Kyoji; Oka, Shinichi; Kimura, Satoshi; Koike, Kazuhiko

    2015-01-01

    Pre-existing low-frequency resistance-associated variants (RAVs) may jeopardize successful sustained virological responses (SVR) to HCV treatment with direct-acting antivirals (DAAs). However, the potential impact of low-frequency (∼0.1%) mutations, concatenated mutations (haplotypes), and their association with genotypes (Gts) on the treatment outcome has not yet been elucidated, most probably owing to the difficulty in detecting pre-existing minor haplotypes with sufficient length and accuracy. Herein, we characterize a methodological framework based on Illumina MiSeq next-generation sequencing (NGS) coupled with bioinformatics of quasispecies reconstruction (QSR) to realize highly accurate variant calling and genotype-haplotype detection. The core-to-NS3 protease coding sequences in 10 HCV monoinfected patients, 5 of whom had a history of blood transfusion, and 11 HCV/HIV coinfected patients with hemophilia, were studied. Simulation experiments showed that, for minor variants constituting more than 1%, our framework achieved a positive predictive value (PPV) of 100% and sensitivities of 91.7–100% for genotyping and 80.6% for RAV screening. Genotyping analysis indicated the prevalence of dominant Gt1a infection in coinfected patients (6/11 vs 0/10, p = 0.01). For clinical samples, minor genotype overlapping infection was prevalent in HCV/HIV coinfected hemophiliacs (10/11) and patients who experienced whole-blood transfusion (4/5) but none in patients without exposure to blood (0/5). As for RAV screening, the Q80K/R and S122K/R variants were particularly prevalent among minor RAVs observed, detected in 12/21 and 6/21 cases, respectively. Q80K was detected only in coinfected patients, whereas Q80R was predominantly detected in monoinfected patients (1/11 vs 7/10, p < 0.01). Multivariate interdependence analysis revealed the previously unrecognized prevalence of Gt1b-Q80K, in HCV/HIV coinfected hemophiliacs [Odds ratio = 13.4 (3.48–51.9), p < 0.01]. Our study

  14. Impact of lopinavir-ritonavir or nevirapine on bedaquiline exposures and potential implications for patients with tuberculosis-HIV coinfection.

    PubMed

    Svensson, Elin M; Dooley, Kelly E; Karlsson, Mats O

    2014-11-01

    Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patients are available. Plasma concentrations of bedaquiline and its M2 metabolite after single doses were obtained from interaction studies with nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects modeling. Potential dose adjustments were evaluated with simulations. No significant effects of nevirapine on bedaquiline pharmacokinetics were identified. LPV/r decreased bedaquiline and M2 clearances to 35% (relative standard error [RSE], 9.2%) and 58% (RSE, 8.4%), respectively, of those without comedication. As almost 3-fold (bedaquiline) and 2-fold (M2) increases in exposures during chronic treatment with LPV/r are expected, dose adjustments are suggested for evaluation. Efficacious, safe bedaquiline dosing for MDR-TB patients receiving antiretrovirals is important. Modeling results suggest that bedaquiline can be coadministered with nevirapine without dose adjustments. The predicted elevation of bedaquiline and M2 levels during LPV/r coadministration may be a safety concern, and careful monitoring is recommended. Further data are being collected in coinfected patients to determine whether dose adjustments are needed. (These studies have been registered at ClinicalTrials.gov under registration numbers NCT00828529 [study C110] and NCT00910806 [study C117].).

  15. Tax gene characterization of human T-lymphotropic virus type 1 strains from Brazilian HIV-coinfected patients.

    PubMed

    Magri, Mariana Cavalheiro; Brigido, Luis Fernando de Macedo; Rodrigues, Rosangela; Morimoto, Helena Kaminami; Caterino-de-Araujo, Adele

    2012-12-01

    The tax gene of human T-lymphotropic virus type 1 (HTLV-1) diverges among isolates according to geographic regions and has been classified into two genotypes: taxA and taxB. In Brazil, taxA is the most prevalent genotype in symptomatic and asymptomatic carriers. Few studies have been conducted in HIV-infected patients. The present study characterized the tax gene (1059 bp) in 13 Brazilian HIV-1/HTLV-1-coinfected patients from the south and southeast regions. The results confirmed the transcontinental HTLV-1 subgroup A of the Cosmopolitan subtype and showed high nucleotide similarity both among Brazilian sequences and in relation to the ATK prototype (99.5% and 99.2%, respectively). Six nucleotide substitutions were highly conserved among isolates, ranging from 76.9% to 100%: C7401T, T7914C, C7920T, C7982T, G8231A, and A8367C. The presence of the Brazilian molecular signature of genotype taxA was confirmed in all of the isolates, and they clustered into two Latin American clusters, which confirms the double introduction of HTLV-1 in Brazil.

  16. Frequent injection cocaine use increases the risk of renal impairment among hepatitis C and HIV coinfected patients

    PubMed Central

    Rossi, Carmine; Cox, Joseph; Cooper, Curtis; Martel-Laferrière, Valérie; Walmsley, Sharon; Gill, John; Sapir-Pichhadze, Ruth; Moodie, Erica E.M.; Klein, Marina B.

    2016-01-01

    Objective: To examine the association between injection cocaine use, hepatitis C virus (HCV) infection, and chronic renal impairment (CRI). Design: Prospective observational cohort study of HIV–HCV coinfected patients. Methods: Data from 1129 participants in the Canadian Co-Infection Cohort with baseline and follow-up serum creatinine measurements between 2003 and 2014 were analyzed. Prevalent and incident cohorts were created to examine the association between self-reported past, current, and cumulative cocaine use and chronic HCV with CRI. CRI was defined as an estimated glomerular filtration rate below 70 ml/min per 1.73 m2. Multivariate logistic regression was used to calculate odds ratios, and discrete-time proportional-hazards models were used to calculate hazard ratios for cocaine use, in the two respective cohorts, adjusted for HCV RNA and important demographic, HIV disease stage, and comorbidity confounders. Results: Eighty-seven participants (8%) had prevalent CRI. Past injection cocaine use was associated with a two-fold greater risk of prevalent CRI [odds ratio 2.03, 95% confidence interval (CI) 0.96, 4.32]. During follow-up, 126 of 1061 participants (12%) developed incident CRI (31 per 1000 person-years). Compared to nonusers, heavy (≥ 3 days/week) and frequent injection cocaine users (≥75% of follow-up time) experienced more rapid progression to CRI (hazard ratio 2.65, 95% CI 1.35, 5.21; and hazard ratio 1.82, 95% CI 1.07, 3.07, respectively). There was no association between chronic HCV and CRI in either cohort. Conclusion: After accounting for HCV RNA, frequent and cumulative injection cocaine abuse was associated with CRI progression and should be taken into consideration when evaluating impaired renal function in HIV–HCV coinfection. PMID:26859371

  17. Predictors of Mortality among Tuberculosis/HIV-Coinfected Persons in Southwest Ethiopia: A Case-Control Study.

    PubMed

    Deribe, Kebede; Yami, Alemeshet; Deribew, Amare; Mesfin, Nebiyu; Colebunders, Robert; Van Geertruyden, Jean Pierre; Woldie, Mirkuzie; Maja, Todd

    2015-01-01

    Tuberculosis (TB) remains the most common cause of death in people living with HIV/AIDS. The aim of the present study was to identify predictors of mortality in TB/HIV-coinfected patients. We conducted an unmatched case-control study among a cohort of TB/HIV-coinfected adults who were on antiretroviral therapy (ART). Cases comprised 69 TB/HIV-coinfected patients who died during this period. For each case, we selected 3 (207) TB/HIV-coinfected patients who were alive during the end of the follow-up period. Male sex (odds ratio [OR] = 2.04, 95% confidence interval [CI]: 1.04-4.02), being bedridden at enrollment (OR = 2.84, 95% CI: 1.17-6.89), and cough of more than 2 weeks during initiation of ART (OR = 4.75 95% CI: 2.14-10.56) were the best predictors of mortality among TB/HIV-coinfected patients. Mortality among TB/HIV-coinfected patients accounted for a considerable number of deaths among the cohort. Patients with cough at ART initiation and with poor functional status should be strictly followed to reduce death. © The Author(s) 2013.

  18. Prevalence of malaria and HIV coinfection and influence of HIV infection on malaria disease severity in population residing in malaria endemic area along the Thai-Myanmar border.

    PubMed

    Rattanapunya, Siwalee; Kuesap, Jiraporn; Chaijaroenkul, Wanna; Rueangweerayut, Ronnatrai; Na-Bangchang, Kesara

    2015-05-01

    The objective of the study is to investigate the prevalence of malaria and HIV coinfection and assess the effect of HIV coinfection on malaria disease severity in malaria patients from the endemic area of Thailand along the Thai-Myanmar border. Blood samples were collected from a total of 867 patients with malaria (all species and severity) who attended Mae Tao clinic for migrant workers, Tak Province during 2005-2007 (439 samples), 2008-2010 (273 samples), and 2011-2013 (155 samples). The average prevalence rate of malaria and HIV coinfected cases in this malaria endemic area of the country during the three periods was 1.85%. HIV coinfection was observed only in samples with mono-infection of Plasmodium falciparum or Plasmodium vivax, with similar proportions (0.81 vs. 1.04%). Patients' admission parasite density, an indicator of disease severity, was significantly higher in cases with HIV coinfection observed during 2008-2010. Anemia was found at a significantly higher frequency in patients coinfected with malaria and HIV observed during 2005-2007 compared with those infected with malaria alone. No association was observed between malaria and HIV coinfection and gender, and infected malaria species during the three observation periods. Patients with malaria and HIV coinfection had a significantly lower hemoglobin level than those with malaria infection alone. In conclusion, the prevalence of malaria and HIV coinfection in population of the malaria endemic area along the Thai-Myanmar border is low. HIV coinfection tended to increase parasite density, an indicator of malaria disease severity.

  19. Pharmacokinetics of para-Aminosalicylic Acid in HIV-Uninfected and HIV-Coinfected Tuberculosis Patients Receiving Antiretroviral Therapy, Managed for Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis

    PubMed Central

    de Kock, Lizanne; Sy, Sherwin K. B.; Diacon, Andreas H.; Prescott, Kim; Hernandez, Kenneth R.; Yu, Mingming; Derendorf, Hartmut; Donald, Peter R.

    2014-01-01

    The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis prompted the reintroduction of para-aminosalicylic acid (PAS) to protect companion anti-tuberculosis drugs from additional acquired resistance. In sub-Saharan Africa, MDR/XDR tuberculosis with HIV coinfection is common, and concurrent treatment of HIV infection and MDR/XDR tuberculosis is required. Out of necessity, patients receive multiple drugs, and PAS therapy is frequent; however, neither potential drug interactions nor the effects of HIV infection are known. Potential drug-drug interaction with PAS and the effect of HIV infection was examined in 73 pulmonary tuberculosis patients; 22 (30.1%) were HIV coinfected. Forty-one pulmonary MDR or XDR tuberculosis patients received 4 g PAS twice daily, and in a second crossover study, another 32 patients were randomized, receiving 4 g PAS twice daily or 8 g PAS once daily. A PAS population pharmacokinetic model in two dosing regimens was developed; potential covariates affecting its pharmacokinetics were examined, and Monte Carlo simulations were conducted evaluating the pharmacokinetic-pharmacodynamic index. The probability of target attainment (PTA) to maintain PAS levels above MIC during the dosing interval was estimated by simulation of once-, twice-, and thrice-daily dosing regimens not exceeding 12 g daily. Concurrent efavirenz (EFV) medication resulted in a 52% increase in PAS clearance and a corresponding >30% reduction in mean PAS area under the concentration curve in 19 of 22 HIV-M. tuberculosis-coinfected patients. Current practice recommends maintenance of PAS concentrations at ≥1 μg/ml (the MIC of M. tuberculosis), but the model predicts that at only a minimum dose of 4 g twice daily can this PTA be achieved in at least 90% of the population, whether or not EFV is concomitantly administered. Once-daily dosing of 12 g PAS will not provide PAS concentrations exceeding the MIC over the entire dosing

  20. Diagnosis, Clinical Presentation, and In-Hospital Mortality of Severe Malaria in HIV-Coinfected Children and Adults in Mozambique

    PubMed Central

    Hendriksen, Ilse C. E.; Ferro, Josefo; Montoya, Pablo; Chhaganlal, Kajal D.; Seni, Amir; Gomes, Ermelinda; Silamut, Kamolrat; Lee, Sue J.; Lucas, Marcelino; Chotivanich, Kesinee; Fanello, Caterina I.; Day, Nicholas P. J.; White, Nicholas J.; von Seidlein, Lorenz; Dondorp, Arjen M.

    2012-01-01

    Background. Severe falciparum malaria with human immunodeficiency virus (HIV) coinfection is common in settings with a high prevalence of both diseases, but there is little information on whether HIV affects the clinical presentation and outcome of severe malaria. Methods. HIV status was assessed prospectively in hospitalized parasitemic adults and children with severe malaria in Beira, Mozambique, as part of a clinical trial comparing parenteral artesunate versus quinine (ISRCTN50258054). Clinical signs, comorbidity, complications, and disease outcome were compared according to HIV status. Results. HIV-1 seroprevalence was 11% (74/655) in children under 15 years and 72% (49/68) in adults with severe malaria. Children with HIV coinfection presented with more severe acidosis, anemia, and respiratory distress, and higher peripheral blood parasitemia and plasma Plasmodium falciparum histidine-rich protein-2 (PfHRP2). During hospitalization, deterioration in coma score, convulsions, respiratory distress, and pneumonia were more common in HIV-coinfected children, and mortality was 26% (19/74) versus 9% (53/581) in uninfected children (P < .001). In an age- and antimalarial treatment–adjusted logistic regression model, significant, independent predictors for death were renal impairment, acidosis, parasitemia, and plasma PfHRP2 concentration. Conclusions. Severe malaria in HIV-coinfected patients presents with higher parasite burden, more complications, and comorbidity, and carries a higher case fatality rate. Early identification of HIV coinfection is important for the clinical management of severe malaria. PMID:22752514

  1. Risk of Hip Fracture Associated with Hepatitis C Virus Infection and Hepatitis C/HIV Coinfection

    PubMed Central

    Re, Vincent Lo; Volk, Jessica; Newcomb, Craig W.; Yang, Yu-Xiao; Freeman, Cristin P.; Hennessy, Sean; Kostman, Jay R.; Tebas, Pablo; Leonard, Mary B.; Localio, A. Russell

    2012-01-01

    Hepatitis C virus (HCV) infection has been associated with reduced bone mineral density, but its association with fracture rates is unknown, particularly in the setting of human immunodeficiency virus (HIV) coinfection. Our objectives were to determine whether persons with HCV infection alone are at increased risk for hip fracture compared to uninfected individuals and to examine if the risk of hip fracture is higher among HCV/HIV-coinfected persons compared to those with HCV alone, those with HIV alone, and those uninfected with either virus. We conducted a cohort study in 36,950 HCV/HIV-coinfected, 276,901HCV-monoinfected, 95,827 HIV-monoinfected, and 3,110,904 HCV/HIV-uninfected persons within the U.S. Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania (1999–2005). Incidence rates of hip fracture were lowest among uninfected persons (1.29 events/1000 person-years), increased with the presence of either HIV infection (1.95 events/1000 person-years) or HCV infection (2.69 events/1000 person-years), and were highest among HCV/HIV-coinfected individuals (3.06 events/1000 person-years). HCV/HIV coinfection was associated with an increased relative hazard (adjusted hazard ratio [95% confidence interval]) of hip fracture compared to HCV-monoinfected (1.38 [1.25–1.53]), HIV-monoinfected (females: 1.76 [1.44–2.16]; males: 1.36 [1.20–1.55]), and uninfected persons (females: 2.65 [2.21–3.17]; males: 2.20 [1.97–2.47]). HCV monoinfection was associated with an increased risk of hip fracture compared to uninfected individuals, and the relative increase was highest in the youngest age groups (females, 18–39 years: 3.56 [2.93–4.32]; males, 18–39 years: 2.40 [2.02–2.84]). Conclusion Among Medicaid enrollees, HCV/HIV coinfection was associated with increased rates of hip fracture compared to HCV-monoinfected, HIV-monoinfected, and HCV/HIV-uninfected persons. HCV-monoinfected patients had an increased risk of hip fracture compared to

  2. Outcome of HCV/HIV-coinfected liver transplant recipients: a prospective and multicenter cohort study.

    PubMed

    Miro, J M; Montejo, M; Castells, L; Rafecas, A; Moreno, S; Agüero, F; Abradelo, M; Miralles, P; Torre-Cisneros, J; Pedreira, J D; Cordero, E; de la Rosa, G; Moyano, B; Moreno, A; Perez, I; Rimola, A

    2012-07-01

    Eighty-four HCV/HIV-coinfected and 252-matched HCV-monoinfected liver transplant recipients were included in a prospective multicenter study. Thirty-six (43%) HCV/HIV-coinfected and 75 (30%) HCV-monoinfected patients died, with a survival rate at 5 years of 54% (95% CI, 42-64) and 71% (95% CI, 66 to 77; p = 0.008), respectively. When both groups were considered together, HIV infection was an independent predictor of mortality (HR, 2.202; 95% CI, 1.420-3.413 [p < 0.001]). Multivariate analysis of only the HCV/HIV-coinfected recipients, revealed HCV genotype 1 (HR, 2.98; 95% CI, 1.32-6.76), donor risk index (HR, 9.48; 95% CI, 2.75-32.73) and negative plasma HCV RNA (HR, 0.14; 95% CI, 0.03-0.62) to be associated with mortality. When this analysis was restricted to pretransplant variables, we identified three independent factors (HCV genotype 1, pretransplant MELD score and centers with <1 liver transplantation/year in HIV-infected patients) that allowed us to identify a subset of 60 (71%) patients with a similar 5-year prognosis (69%[95% CI, 54-80]) to that of HCV-monoinfected recipients. In conclusion, 5-year survival in HCV/HIV-coinfected liver recipients was lower than in HCV-monoinfected recipients, although an important subset with a favorable prognosis was identified in the former. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  3. Ledipasvir-sofosbuvir for 6 weeks to treat acute hepatitis C virus genotype 1 or 4 infection in patients with HIV coinfection: an open-label, single-arm trial.

    PubMed

    Rockstroh, Jürgen K; Bhagani, Sanjay; Hyland, Robert H; Yun, Chohee; Dvory-Sobol, Hadas; Zheng, Wei; Brainard, Diana M; Ingiliz, Patrick; Lutz, Thomas; Boesecke, Christoph; Nelson, Mark

    2017-05-01

    The latest European Association for the Study of the Liver (EASL) guidelines now recommend that patients with acute hepatitis C virus (HCV) infection should be treated with a combination of sofosbuvir and an NS5A inhibitor for 8 weeks. However, the ideal duration of treatment with interferon-free regimens, particularly in HIV-coinfected individuals, remains unknown. We assessed the efficacy and safety of 6 weeks of ledipasvir-sofosbuvir for acute genotype 1 or 4 HCV in HIV-1-coinfected patients. This open-label, single-arm trial, done in Germany and the UK, included patients with acute HCV genotype 1 or 4 and HIV-1. At screening, patients were either receiving HIV antiretrovirals and had HIV RNA less than 200 copies per mL, or not receiving antiretrovirals and had a CD4 T-cell count of greater than 500 cells per μL. All patients received ledipasvir-sofosbuvir once daily for 6 weeks. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after the end of treatment (SVR12). This study is registered with ClinicalTrials.gov, number NCT02457611. Between June 11, 2015, and Jan 8, 2016, we enrolled and treated 26 patients. All (100%) were men, 24 (92%) were white, and 25 (96%) were receiving antiretroviral treatment. 19 (73%) had genotype 1a and seven (27%) had genotype 4 HCV. Overall, 20 (77%; 95% CI 56-91) of 26 patients achieved SVR12: 15 (79%) of 19 with genotype 1a, and five (71%) of seven with genotype 4. Of six patients not achieving SVR12, three relapsed, two achieved sustained virological response 4 weeks after the end of treatment but were lost to follow-up, and one was reinfected. The most common adverse events were fatigue (seven participants [27%]), nasopharyngitis (seven [27%]), and headache (six [23%]). No patient discontinued or interrupted therapy due to adverse events. No HIV rebound occurred during the study. The rate of cure with a fixed-dose combination of ledipasvir-sofosbuvir for patients with

  4. Regression of liver fibrosis is progressive after sustained virological response to HCV therapy in patients with hepatitis C and HIV coinfection.

    PubMed

    Casado, J L; Quereda, C; Moreno, A; Pérez-Elías, M J; Martí-Belda, P; Moreno, S

    2013-12-01

    There are few data about the long-term histological outcome of HIV-/HCV-coinfected patients after therapy with interferon and ribavirin. We performed an observational study of 216 patients who received therapy against HCV and who had at least three successive transient elastographies (TE) during the follow-up. The primary endpoint was confirmed fibrosis regression, defined as a reduction of at least 1 point in Metavir fibrosis score, confirmed and without worsening in successive TE. At baseline, 23% had fibrosis stage 4 or cirrhosis. Overall, 82 (38%) achieved sustained virological response (SVR), without differences in baseline fibrosis or time of follow-up. Confirmed fibrosis regression was observed in 55% of patients, higher for SVR (71% vs 44%; P < 0.01), and the likelihood of achieving fibrosis regression at 3, 5 and 7 years was 0.17, 0.51 and 0.67, respectively, for SVR patients, in comparison with 0.02, 0.23 and 0.41 for no SVR patients (P < 0.01, log-rank test at any time point). Progressive regression, defined as continuous improvement in successive TE, was observed in 62% of patients with advanced liver fibrosis or cirrhosis who achieved SVR. In a Cox regression model, only SVR (HR, 4.01; 95% CI, 2.33-7.57; P < 0.01) and a younger age (HR, 1.14; 95% CI, 1.05-1.25; P < 0.01; per year) were associated with fibrosis regression. This study confirms that the rate of liver fibrosis regression increases during the follow-up after SVR to interferon therapy in HIV-/HCV-coinfected patients.

  5. Hepatitis B Virus Genotype Distribution and Its Lamivudine-Resistant Mutants in HIV-Coinfected Patients with Chronic and Occult Hepatitis B

    PubMed Central

    Quarleri, J.; Moretti, F.; Bouzas, M.B.; Laufer, N.; Carrillo, M. Gómez; Giuliano, S. Fernández; Pérez, H.; Cahn, P.; Salomon, H.

    2010-01-01

    Hepatitis B virus (HBV) genotypes were examined in HIV-infected patients with chronic and occult HBV infection. From a total population of 593 HIV-infected patients, 22 individuals (prevalence 3.7%) were found to be HBsAg while 72 (12.1%) were found to be anti-HBc alone. From them, 20 and 4 were HBV DNA positive, respectively. These last four patients are therefore considered to be HBV infected in an occult form. The genotypes could be determined in all 24 HBV-infected patients. HBV-A was the most common (20/24; 83.3%), followed by HBV-D (2/24; 8.3%) and HBV-F (1/24; 4.2%). The remaining sample exhibited mixed infection involving genotypes A and D as pure ones, thus also forming part of three intergenotypic recombinant forms exhibiting different mosaic S gene patterns. The sexual route of transmission was predominant among HBV genotype A-infected patients. Among the 24 HBV DNA-positive patients, point mutations related to lamivudine resistance were found in four strains. These viral strains showed a methionine-to-valine substitution at codon 204 (rtM204V) in association with an upstream B-domain change at rtL180M. Additionally, two of them exhibited the additional rtV173L mutation. The value of HBV molecular monitoring including both HBV viral genomic characterization and genotypic resistance profile in HIV-HBV-coinfected individuals is discussed. PMID:17506609

  6. Addressing tuberculosis in the context of malnutrition and HIV coinfection.

    PubMed

    Semba, Richard D; Darnton-Hill, Ian; de Pee, Saskia

    2010-12-01

    Tuberculosis is the second leading cause of infectious disease mortality (1.8 million/year), after HIV/AIDS. There are more than 9 million new cases each year. One-third of the world's population, and 50% of adults in sub-Saharan Africa, South Asia, and SouthEast Asia, are infected, representing an enormous pool of individuals at risk for developing the disease. The situation is complicated by the HIV/AIDS pandemic, widespread undernutrition, smoking, diabetes, increased mobility, and emergence of multi- and extensively drug-resistant tuberculosis. To review the scientific evidence about the interactions among tuberculosis, nutrition, and HIV coinfection. HIV infection and malnutrition lower immunity, increasing the risk of reactivation tuberculosis and primary progressive disease. Having either tuberculosis or HIV infection causes weight loss. Malnutrition markedly increases mortality among both tuberculosis and HIV/AIDS patients and should be treated concurrently with treatment of the infections. Tuberculosis treatment is a prerequisite for nutritional recovery, in addition to intake of nutrients required for rebuilding tissues, which is constrained in food-insecure households. Additional pharmaceutical treatment to reduce the catabolic impact of inflammation or promote growth may be needed. Specific nutrients can contribute to faster sputum smear clearance, which is important for reducing transmission, as well as faster weight gain when combined with an adequate diet. Adequate nutrition and weight gain in undernourished populations might reduce the incidence of tuberculosis. The many risk factors for the development of tuberculosis need to be addressed simultaneously, especially HIV/AIDS and food insecurity and undernutrition. For stronger evidence-based guidelines, existing recommendations and clinical applications need to be more widely applied and evaluated.

  7. Addressing tuberculosis in the context of malnutrition and HIV coinfection.

    PubMed

    Semba, Richard D; Darnton-Hill, Ian; de Pee, Saskia

    2010-12-01

    Tuberculosis is the second leading cause of infectious disease mortality (1.8 million/year), after HIV/AIDS. There are more than 9 million new cases each year. One-third of the world's population, and 50% of adults in sub-Saharan Africa, South Asia, and South-East Asia, are infected, representing an enormous pool of individuals at risk for developing the disease. The situation is complicated by the HIV/AIDS pandemic, widespread undernutrition, smoking, diabetes, increased mobility, and emergence of multi- and extensively drug-resistant tuberculosis. To review the scientific evidence about the interactions among tuberculosis, nutrition, and HIV coinfection. HIV infection and malnutrition lower immunity, increasing the risk of reactivation tuberculosis and primary progressive disease. Having either tuberculosis or HIV infection causes weight loss. Malnutrition markedly increases mortality among both tuberculosis and HIV/AIDS patients and should be treated concurrently with treatment of the infections. Tuberculosis treatment is a prerequisite for nutritional recovery, in addition to intake of nutrients required for rebuilding tissues, which is constrained in food-insecure households. Additional pharmaceutical treatment to reduce the catabolic impact of inflammation or promote growth may be needed. Specific nutrients can contribute to faster sputum smear clearance, which is important for reducing transmission, as well as faster weight gain when combined with an adequate diet. Adequate nutrition and weight gain in undernourished populations might reduce the incidence of tuberculosis. CONCLUSIONS; The many risk factors for the development of tuberculosis need to be addressed simultaneously, especially HIV/AIDS and food insecurity and undernutrition. For stronger evidence-based guidelines, existing recommendations and clinical applications need to be more widely applied and evaluated.

  8. Perceived quality of life among Visceral Leishmaniasis and HIV coinfected migrant male-workers in Northwest Ethiopia: a qualitative study.

    PubMed

    Alemayehu, Mekuriaw; Wubshet, Mamo; Mesfin, Nebiyu; Gebayehu, Abebaw

    2017-02-16

    There is paucity of data on quality of life as a dimension of treatment outcome among Visceral Leishmaniasis and HIV coinfected patients. This study sought to explore perceived quality of life among Visceral Leishmaniasis and HIV coinfected male migrant workers in Northwest Ethiopia. Twenty Visceral Leishmaniasis and HIV coinfected study participants took part in the in-depth interviews at Visceral Leishmaniasis and HIV treatment centers. Ten participants were on antiretroviral treatment (ART) and the remaining 10 have not yet started ART. All interviews were recorded, transcribed and translated for analysis. Data were analyzed by qualitative content analysis using Open Code software version 3.4. Participants reported on four aspects of quality of life: liveability of the environment, utility of life, life ability of a person and appreciation of life. Respondents living environment, therapeutic side effects of Visceral Leishmaniasis drugs, poverty and stigma negatively affected their quality of life. On the contrary, good treatment response and financial security were reported to positively affect their quality of life. Challenges related to the living environment, financial limitations and sub-optimal response of Visceral Leishmaniasis drug and relapse of Visceral Leishmaniasis disease are factors most negatively affecting the quality of life of Visceral Leishmaniasis and HIV coinfected patients. Micro-financing and other socio-economical support programs should be launched to assist the unemployed males migrating to Visceral Leishmaniasis endemic and relatively higher HIV prevalent areas to work as daily laborers. HIV prevention programs in HIV positive-living counseling programs should target such high risk migrant workers in the endemic areas.

  9. Cryoglobulinaemia associated with hepatitis C virus: influence of HCV genotypes, HCV-RNA viraemia and HIV coinfection.

    PubMed

    Ramos-Casals, M; Forns, X; Brito-Zerón, P; Vargas, A; Ruiz, M; Laguno, M; Yagüe, J; Sánchez-Tapias, J M; Gatell, J M; Font, J

    2007-10-01

    To determine whether the clinical and immunological expression of patients with cryoglobulinaemia associated with chronic hepatitis C virus (HCV) infection varied according to HCV-RNA load, HCV genotype or human immunodeficiency virus (HIV) coinfection. We studied 340 HCV patients (188 women and 152 men, with a mean age of 49 years) consecutively diagnosed with cryoglobulinaemia between 1993 and 2003 in our hospital. HCV infection was confirmed by serum HCV-RNA determination in all patients. Two hundred and forty-eight (73%) patients had asymptomatic cryoglobulinaemia and 92 (27%) presented cryoglobulinaemic symptoms. Patients with genotype 1 had a higher mean age at diagnosis of cryoglobulinaemia (48.2 vs 40.2 yrs, P < 0.001) and a higher prevalence of cryoglobulinaemic symptoms (25%vs 10%, P = 0.02), especially of vasculitic features (19%vs 5%, P = 0.014). In comparison with monoinfected HCV patients, those with HIV coinfection had a lower mean age at diagnosis of cryoglobulinaemia (40.4 vs 52.8 years, P < 0.001), a lower prevalence of cryoglobulinaemic symptoms (15%vs 34%, P < 0.001), vasculitis (10%vs 28%, P < 0.001), associated systemic autoimmune disease (3%vs 14%, P = 0.001), rheumatoid factor (30%vs 70%, P = 0.001) and hypocomplementaemia (50%vs 78%, P = 0.01). In HCV-HIV patients, a high viral load was associated with a high frequency of symptomatic cryoglobulinaemia, especially in patients with a high viral load of the two viruses (50%vs 7%, P = 0.001) A higher frequency of cryoglobulinaemic symptoms (especially vasculitis) was found in patients with HCV monoinfection and in those carrying HCV genotype 1. In contrast, patients with HIV coinfection presented a threefold lower prevalence of vasculitis. Associated HIV infection significantly attenuated the clinical and immunological expression of cryoglobulinaemia, except in coinfected patients with high viral loads for the two viruses.

  10. Pharmacogenomic study in patients with multiple sclerosis: Responders and nonresponders to IFN-β.

    PubMed

    Bustamante, Marta F; Morcillo-Suárez, Carlos; Malhotra, Sunny; Rio, Jordi; Leyva, Laura; Fernández, Oscar; Zettl, Uwe K; Killestein, Joep; Brassat, David; García-Merino, Juan Antonio; Sánchez, Antonio J; Urcelay, Elena; Alvarez-Lafuente, Roberto; Villar, Lusia M; Alvarez-Cermeño, Jose Carlos; Farré, Xavier; Lechner-Scott, Jeannette; Vandenbroeck, Koen; Rodríguez-Antigüedad, Alfredo; Drulovic, Jelena S; Martinelli Boneschi, Filippo; Chan, Andrew; Oksenberg, Jorge; Navarro, Arcadi; Montalban, Xavier; Comabella, Manuel

    2015-10-01

    We aimed to investigate the association between polymorphisms located in type I interferon (IFN)-induced genes, genes belonging to the toll-like receptor (TLR) pathway, and genes encoding neurotransmitter receptors and the response to IFN-β treatment in patients with multiple sclerosis (MS). In a first or screening phase of the study, 384 polymorphisms were genotyped in 830 patients with MS classified into IFN-β responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-β response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-β responders and 274 nonresponders). Seven single nucleotide polymorphisms (SNPs) were selected from the screening phase for further validation: rs832032 (GABRR3; p = 0.0006), rs6597 (STUB1; p = 0.019), rs3747517 (IFIH1; p = 0.010), rs2277302 (PELI3; p = 0.017), rs10958713 (IKBKB; p = 0.003), rs2834202 (IFNAR1; p = 0.030), and rs4422395 (CXCL1; p = 0.017). None of these SNPs were significantly associated with IFN-β response when genotyped in an independent cohort of patients. Combined analysis of these SNPs in all patients with MS (N = 1,385) revealed 2 polymorphisms associated with IFN-β response: rs2277302 (PELI3; p = 0.008) and rs832032 (GABRR3; p = 0.006). These findings do not support an association between polymorphisms located in genes related to the type I IFN or TLR pathways or genes encoding neurotransmitter receptors and the clinical response to IFN-β. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted.

  11. Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode

    PubMed Central

    Belzeaux, R; Bergon, A; Jeanjean, V; Loriod, B; Formisano-Tréziny, C; Verrier, L; Loundou, A; Baumstarck-Barrau, K; Boyer, L; Gall, V; Gabert, J; Nguyen, C; Azorin, J-M; Naudin, J; Ibrahim, E C

    2012-01-01

    To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis. PMID:23149449

  12. Treat Early or Wait and Monitor? A Qualitative Analysis of Provider Hepatitis C Virus Treatment Decision-Making in the Context of HIV Coinfection

    PubMed Central

    Ryan, Gery; Osilla, Karen Chan; Bhatti, Laveeza; Goetz, Matthew; Witt, Mallory

    2009-01-01

    Abstract Liver disease is a leading cause of death among patients with HIV coinfected with hepatitis C (HCV); yet, studies show that less than 10% receive HCV treatment, in part because of limited treatment response, high treatment toxicity, and psychosocial barriers to treatment readiness. Using a process model framework, we sought to explore the factors and processes by which providers make HCV treatment decisions for HIV-coinfected patients. We conducted 22 semistructured interviews with primary care providers and support staff at three HIV clinics in Los Angeles, California, in which rates of HCV treatment uptake varied from 10% to 38%. Providers agreed that stable HIV disease, favorable genotype, and significant signs of liver disease progression are all signs of need for treatment. However, two divergent treatment approaches emerged for genotype 1 and 4 patients with minimal disease, and in definitions of patient readiness. Providers with lower treatment rates preferred to delay treatment in hopes of better future treatment options, and were more conservative in requiring complete mental health screens and treatment and abstinence from substance use. Conversely, providers with higher treatment rates viewed all patients as needing treatment as soon as possible, and defined readiness more leniently, with some willing to treat even in the context of untreated depression and drug use, so long as ability to adhere well was demonstrated. Regardless of whether an aggressive or cautious approach to treatment is used, development of effective programs for promoting patient treatment readiness is critical to ensuring greater treatment uptake. PMID:19663714

  13. Minoxidil dose response study in female pattern hair loss patients determined to be non-responders to 5% topical minoxidil.

    PubMed

    McCoy, J; Goren, A; Kovacevic, M; Shapiro, J

    2016-01-01

    Topical minoxidil is the only US FDA approved drug for the treatment of female pattern hair loss (FPHL). 5% minoxidil foam is only effective at re-growing hair in a minority of women (approximately 40%). Thus, the majority of FPHL patients remain untreated. Previously, we demonstrated that nonresponders to 5% minoxidil have low metabolism of minoxidil in hair follicles. As such, we hypothesized that increasing the dosage of topical minoxidil to low metabolizers would increase the number of responders without increasing the incidence of adverse events. In this study, we recruited FPHL subjects that were identified as non-responders to 5% topical minoxidil utilizing the previously validated assay for minoxidil response. Subjects were treated for 12 weeks with a novel 15% topical minoxidil solution. At 12 weeks, 60% of subjects achieved a clinically significant response based on target area hair counts (>13.7% from baseline), as well as significant improvement in global photographic assessment. None of the subjects experienced significant hemodynamic changes or any other adverse events. To the best of our knowledge, this is the first study to demonstrate the potentially beneficial effect of a higher dosage of minoxidil in FPHL subjects who fail to respond to 5% minoxidil.

  14. Stronger hepatitis C virus-specific CD8+ T-cell responses in HIV coinfection.

    PubMed

    Barrett, L; Gallant, M; Howley, C; Ian Bowmer, M; Hirsch, G; Peltekian, K; Grant, M

    2011-03-01

    Hepatitis C virus (HCV) is a widespread chronic infection that shares routes of transmission with human immunodeficiency virus (HIV). Thus, coinfection with these viruses is a relatively common and growing problem. In general, liver disease develops over years with HIV coinfection, when compared to decades in HCV monoinfection. The role of the immune system in the accelerated pathogenesis of liver disease in HIV/HCV coinfection is not clear. In this study, we compared the frequency, magnitude, breadth and specificity of peripheral blood CD4+ and CD8+ T-cell responses between HCV-monoinfected and HCV/HIV-coinfected individuals and between HIV/HCV-coinfected subgroups distinguished by anti-HCV antibody and HCV RNA status. While HIV coinfection tended to reduce the frequency and breadth of anti-HCV CD8+ T-cell responses in general, responses that were present were substantially stronger than in monoinfection. In all groups, HCV-specific CD4+ T-cell responses were rare and weak, independent of either nadir or concurrent CD4+ T-cell counts of HIV-infected individuals. Subgroup analysis demonstrated restricted breadth of CD8+ HCV-specific T-cell responses and lower B-cell counts in HIV/HCV-coinfected individuals without anti-HCV antibodies. The greatest difference between HIV/HCV-coinfected and HCV-monoinfected groups was substantially stronger HCV-specific CD8+ T-cell responses in the HIV-coinfected group, which may relate to accelerated liver disease in this setting.

  15. Sildenafil failures may be due to inadequate patient instructions and follow-up: a study on 100 non-responders.

    PubMed

    Hatzichristou, Dimitrios; Moysidis, Kyriakos; Apostolidis, Apostolos; Bekos, Athanasios; Tzortzis, Vasilios; Hatzimouratidis, Konstantinos; Ioannidis, Evangelos

    2005-04-01

    The objective of this study was to identify factors that affect efficacy response rate to sildenafil in the clinical practice. The study comprised 100 consecutive sildenafil non-responders. Mean patient age was 59+/-14.4 years and mean duration of ED 5.5+/-6.4 years. All patients underwent detailed medical and sexual history and completed the IIEF and a questionnaire regarding the previous use of sildenafil. When inadequate instructions were reported, information on the appropriate use of sildenafil was given and patients were asked to use at least 4 tablets at home. Pharmacologic efficacy was re-evaluated in a scheduled follow-up visit. Mean Erectile Function Domain (ED) of the IIEF score was 14+/-9.9. In 56 patients inappropriate use of sildenafil was recognized; 45 had never used the highest recommended dose (100 mg), 32 had taken the pill with a full stomach right after a meal, 22 had taken the pill just before the initiation of sexual activity and 12 were not aware that sexual stimulation was mandatory to achieve an erection. Furthermore, 8 patients had tried the 100mg dose, despite the presence of factors associated with sildenafil clearance reduction (renal insufficiency, cimetidine treatment). Only 34 patients reported that their physician had scheduled a follow-up visit. Following adequate dose titration and time adjustment, 31 patients responded to sildenafil; 10 patients used the 50 mg dose and 21 the 100 mg. Second and third-line treatment options were offered to the rest of the patients. ED patients may receive inadequate instructions with their prescriptions. Response rate to sildenafil may be maximized after receiving appropriate dose titration and instructions on administration. ED should be treated in the same way as other chronic conditions; follow-up is necessary to evaluate the appropriate application and pharmacologic efficacy of the proposed treatment.

  16. Nonresponder anorectic patients after 6 months of multimodal treatment: predictors of outcome.

    PubMed

    Fassino, S; Abbate Daga, G; Amianto, F; Leombruni, P; Garzaro, L; Rovera, G G

    2001-12-01

    Currently the therapy of anorexia nervosa is a relevant clinical problem. The percentage of patients who respond to short-term pharmacotherapy and psychotherapy is still low and the condition often leads to chronic pathology or death. The present study aims to determine outcome predictors beyond personality traits, eating psychopathology, or particular clinical features. Forty patients with restricter type anorexia nervosa were tested, at T0 and after 180 days, with psychometric tests and clinical evaluation instruments. Patients were then divided into two groups. One group included patients who showed relevant clinical improvement; the other included not-yet-improved patients. A lower Novelty Seeking, higher levels of Ascetism and Maturity Fears characterised the not-yet-improved group. Correlation showed evidence of diverse bonds between personality and psychopathology in the improved and not-yet-improved groups. The psychopathology of non-yet-improved patients seemed to be more linked to their temperamental features, whereas improved patients seemed to be more influenced by their character. Different levels of psychological functioning can be expressed. The present data suggest focusing pharmacotherapy and psychotherapy, even family counseling, with a progression more strictly related to the current personality functioning level and psychopathology of each patient.

  17. Tuberculosis and HIV coinfection in Europe: looking at one reality from two angles

    PubMed Central

    van der Werf, Marieke J.; Ködmön, Csaba; Zucs, Phillip; Hollo, Vahur; Amato-Gauci, Andrew J.; Pharris, Anastasia

    2016-01-01

    Objective: To better understand the epidemiology of tuberculosis (TB)/HIV coinfection in the European Union (EU) and European Economic Area (EEA) for planning of prevention and control measures. Design: Analysis of surveillance data. Methods: We performed an analysis of the 2014 TB and AIDS data to assess the burden of TB/HIV coinfection and we applied multivariable logistic regression to evaluate predictors for coinfection. Results: Twenty-one of 31 EU/EEA countries reported HIV testing results for 64.6% of the 32 892 notified TB cases. Of those, 1051 (4.9%) were reported as HIV-positive. Males [adjusted odds ratio (aOR) 1.25; 95% confidence interval (CI) 1.07–1.46] and those in age group 25–44 years were more frequently coinfected. TB cases originating from the WHO African region had the highest proportion of coinfection (aOR 3.28 versus origin in EU/EEA; 95% CI 2.35–4.57). TB treatment was completed successfully by 57.9% of HIV-positive TB cases and 83.5% of HIV-negative cases. In 2014, 3863 cases of AIDS were reported by 29 EU/EEA countries; 691 (17.9%) of these cases presented with TB as an AIDS-defining illness. Persons who had acquired HIV through injecting drug use had higher odds of TB as an AIDS-defining illness (aOR 1.78 versus heterosexual route of transmission; 95% CI 1.37–2.32). Conclusion: TB/HIV coinfection is a substantial problem in the EU/EEA. The occurrence of TB in HIV-positive cases and the low TB treatment success rate suggest that international guidelines for prevention and treatment of TB in HIV-infected adults need to be better implemented. PMID:27755106

  18. Consensus interferon and ribavirin in patients with chronic hepatitis C who were nonresponders to pegylated interferon alfa-2b and ribavirin.

    PubMed

    Leevy, Carroll B

    2008-07-01

    Recent studies suggest that consensus interferon and ribavirin is effective in retreating patients with chronic hepatitis C who failed therapy with interferon alfa and ribavirin. The objective of the present study was to assess the efficacy, safety, and tolerability of consensus interferon and ribavirin in patients who did not respond to pegylated interferon alfa-2b and ribavirin. We retrospectively identified 137 consecutive nonresponders to pegylated interferon alfa-2b and ribavirin and initiated patients on daily treatment with consensus interferon 15 mug subcutaneously and weight-based ribavirin for 48 weeks. If patients were HCV RNA negative at 12 weeks, the dose was reduced to 15 mug three times weekly for the remaining 36 weeks. The sustained virologic response rate was 37%. Daily consensus interferon therapy was safe and well tolerated in all patients. No dose reductions were required, and no patient discontinued therapy. Further studies of consensus interferon and ribavirin in nonresponders are warranted.

  19. CD4+ T-cell-independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection.

    PubMed

    Foreman, Taylor W; Mehra, Smriti; LoBato, Denae N; Malek, Adel; Alvarez, Xavier; Golden, Nadia A; Bucşan, Allison N; Didier, Peter J; Doyle-Meyers, Lara A; Russell-Lodrigue, Kasi E; Roy, Chad J; Blanchard, James; Kuroda, Marcelo J; Lackner, Andrew A; Chan, John; Khader, Shabaana A; Jacobs, William R; Kaushal, Deepak

    2016-09-20

    The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4(+) T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtb replication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4(+) T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8(+) memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV- and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies.

  20. Stroke and aspirin non-responder patients: relation with hypertension and platelet response to adenosine diphosphate.

    PubMed

    Godeneche, G; Sorel, N; Ragot, S; Chomel, J C; Neau, J P; Macchi, L

    2009-11-01

    Despite its widespread use, there are many concerns about the efficacy of aspirin in the secondary prevention of cardiovascular events after stroke, leading to the concept of aspirin non-response (ANR). Although the mechanisms of ANR remain uncertain, it is expected to be due to a combination of clinical, biological and genetic characteristics affecting platelet function. In this study, we investigated whether clinical and/or biological factors such as hypertension and platelet response to ADP could contribute to the ANR. As a secondary objective, we determine whether ANR and collagen/ADP closure time (CADP-CT) could be related to platelet glycoprotein single nucleotide polymorphisms (SNPs). One hundred patients on aspirin (160 mg/day) were enrolled. ANR was measured with a platelet function analyzer (PFA-100); genotyping of four SNPs (GP IIIa, GP Ia, P2Y12 and GP VI) was performed using a tetra-primer amplification refractory mutation system. Using a collagen/epinephrine-coated cartridge on the PFA-100, the prevalence of ANR was 15% (n = 15). In the ANR group, (i) CADP-CT was significantly shorter and (ii) hypertension was an independent clinical predictive factor of ANR (OR = 4.25; 95%CI: 1.06-17.11). No clear relation was found between CADT-CT and platelet gene polymorphism as well as ANR status and SNPs. In conclusion our study confirms the independent relationship between hypertension, platelet hypersensitivity to ADP and aspirin (160 mg/day) non-response. The differential sensitivity to aspirin may have potential clinical implications, where adaptation of antiplatelet therapy is necessary according to a patient's clinical and genetic characteristics.

  1. Mucocutaneous Leishmaniasis/HIV Coinfection Presented as a Diffuse Desquamative Rash

    PubMed Central

    da Silva, Guilherme Almeida Rosa; Sugui, Daniel; Nunes, Rafael Fernandes; de Azevedo, Karime; de Azevedo, Marcelo; Marques, Alexandre; Martins, Carlos; Ferry, Fernando Raphael de Almeida

    2014-01-01

    Leishmaniasis is an infectious disease that is endemic in tropical areas and in the Mediterranean. This condition spreads to 98 countries in four continents, surpassing 12 million infected individuals, with 350 million people at risk of infection. This disease is characterized by a wide spectrum of clinical syndromes, caused by protozoa of the genus Leishmania, with various animal reservoirs, such as rodents, dogs, wolves, foxes, and even humans. Transmission occurs through a vector, a sandfly of the genus Lutzomyia. There are three main clinical forms of leishmaniasis: visceral leishmaniasis, cutaneous leishmaniasis, and mucocutaneous leishmaniasis. The wide spectrum of nonvisceral forms includes: localized cutaneous leishmaniasis, a papular lesion that progresses to ulceration with granular base and a large framed board; diffuse cutaneous leishmaniasis; mucocutaneous leishmaniasis, which can cause disfiguring and mutilating injuries of the nasal cavity, pharynx, and larynx. Leishmaniasis/HIV coinfection is considered an emerging problem in several countries, including Brazil, where, despite the growing number of cases, a problem of late diagnosis occurs. Clinically, the cases of leishmaniasis associated with HIV infection may demonstrate unusual aspects, such as extensive and destructive lesions. This study aims to report a case of mucocutaneous leishmaniasis/HIV coinfection with atypical presentation of diffuse desquamative eruption and nasopharyngeal involvement. PMID:25548691

  2. Cerebral blood flow in obsessive-compulsive patients with major depression: effect of treatment with sertraline or desipramine on treatment responders and non-responders.

    PubMed

    Hoehn-Saric, R; Schlaepfer, T E; Greenberg, B D; McLeod, D R; Pearlson, G D; Wong, S H

    2001-11-30

    We examined the effects of sertraline and of desipramine on patients with OCD and comorbid major depressive episodes at study entry. Sixteen patients, 9 receiving sertraline and 7 desipramine, received HMPAO SPECT scans while free of medication and after 12 weeks of treatment. Patients on sertraline showed significantly reduced regional cerebral blood flow (rCBF) in the right prefrontal and temporal regions. Patients on desipramine showed more diffuse rCBF reductions in frontal and temporal regions, more so in the left side. In a second analysis, patients who had a symptom reduction on the Yale-Brown Obsessive Compulsive Scale (YBOCS), irrespective of the type of medication, were retrospectively classified as 'responders' to treatment. Eleven patients were 'responders' and 5 'non-responders'. Before being medicated, responders differed from non-responders through higher rCBF in prefrontal regions, mostly on the left, and higher rCBF in the cingulate and basal ganglia bilaterally. After 12 weeks of treatment, responders showed a diffuse reduction of rCBF in prefrontal regions while non-responders showed only a few scattered low-frequency responses. Thus, higher prefrontal and subcortical activity was associated with better response to drug treatment. In addition, clinical change, but not the administration of medication as such, was associated with a decrease of prefrontal rCBF.

  3. Plasma Levels of Neopterin and C-Reactive Protein (CRP) in Tuberculosis (TB) with and without HIV Coinfection in Relation to CD4 Cell Count.

    PubMed

    Skogmar, Sten; Schön, Thomas; Balcha, Taye Tolera; Sturegård, Erik; Jansson, Marianne; Björkman, Per

    2015-01-01

    While the risk of TB is elevated in HIV-positive subjects with low CD4 cell counts, TB may in itself be associated with CD4 lymphocytopenia. We investigated markers of immune activation (neopterin) and inflammation (CRP) in TB patients with and without HIV coinfection and their association with CD4 cell levels, and determined their predictive capacity as alternative markers of advanced immunosuppression. Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The performance to predict CD4 cell strata for both markers were investigated using receiver operating curves. Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 μg/ml, HIV-/TB+ 33 μg/ml, controls 0.5 μg/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers had adequate predictive value for identification of subjects with CD4 cell count <100 cells/mm3 (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP). Neopterin levels were high in adults with TB, both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as alternative tests for immunosuppression in patients coinfected with HIV and TB.

  4. Plasma Levels of Neopterin and C-Reactive Protein (CRP) in Tuberculosis (TB) with and without HIV Coinfection in Relation to CD4 Cell Count

    PubMed Central

    Skogmar, Sten; Schön, Thomas; Balcha, Taye Tolera; Sturegård, Erik; Jansson, Marianne; Björkman, Per

    2015-01-01

    Background While the risk of TB is elevated in HIV-positive subjects with low CD4 cell counts, TB may in itself be associated with CD4 lymphocytopenia. We investigated markers of immune activation (neopterin) and inflammation (CRP) in TB patients with and without HIV coinfection and their association with CD4 cell levels, and determined their predictive capacity as alternative markers of advanced immunosuppression. Methods Participants selected from a cohort of adults with TB at Ethiopian health centers (195 HIV+/TB+, 170 HIV-/TB+) and 31 controls were tested for plasma levels of neopterin and CRP. Baseline levels of neopterin and CRP were correlated to CD4 cell count before and after anti-TB treatment (ATT). The performance to predict CD4 cell strata for both markers were investigated using receiver operating curves. Results Levels of both biomarkers were elevated in TB patients (neopterin: HIV+/TB+ 54 nmol/l, HIV-/TB+ 23 nmol/l, controls 3.8 nmol/l; CRP: HIV+/TB+ 36 μg/ml, HIV-/TB+ 33 μg/ml, controls 0.5 μg/ml). Neopterin levels were inversely correlated (-0.53, p<0.001) to CD4 cell count, whereas this correlation was weaker for CRP (-0.25, p<0.001). Neither of the markers had adequate predictive value for identification of subjects with CD4 cell count <100 cells/mm3 (area under the curve [AUC] 0.64 for neopterin, AUC 0.59 for CRP). Conclusion Neopterin levels were high in adults with TB, both with and without HIV coinfection, with inverse correlation to CD4 cell count. This suggests that immune activation may be involved in TB-related CD4 lymphocytopenia. However, neither neopterin nor CRP showed promise as alternative tests for immunosuppression in patients coinfected with HIV and TB. PMID:26630153

  5. Changes in lumbar multifidus muscle function and nociceptive sensitivity in low back pain patient responders versus non-responders after dry needling treatment.

    PubMed

    Koppenhaver, Shane L; Walker, Michael J; Su, Jonathan; McGowen, Jared M; Umlauf, Lindsey; Harris, Kevin D; Ross, Michael D

    2015-12-01

    Little is known about the physiologic mechanism of dry needling. While some evidence suggests that dry needling may decrease nocioceptive sensitivity and facilitate muscle function, no studies to date have examined these physiologic changes compared to clinical outcomes. To examine changes in lumbar multifidus (LM) muscle function and nociceptive sensitivity after dry needling in patients with LBP and to determine if such changes differ in patients that exhibit improved disability (responders) and those that do not (non-responders). Quasi-experimental study. Sixty-six volunteers with mechanical LBP (38 men, age = 41.3 ± 9.2 years) completed the study. Ultrasound measurements and pain algometry of the LM were taken at baseline and repeated immediately following dry needling treatment to the LM muscles and after one week. The percent change in muscle thickness from rest to contraction was calculated for each time point to represent muscle function. Pressure pain threshold (PPT) was used to measure nociceptive sensitivity. Participants were dichotomized as responders and non-responders based on whether or not they experienced clinical improvement using the modified Oswestry Disability Index after one week. 2 × 3 mixed-model ANOVA were conducted for group (responders vs. non-responders) by time. Patient responders exhibited larger improvements in LM muscle contraction and nociceptive sensitivity 1 week, but not immediately, after dry needling than non-responders. Our results suggest that there may be lasting and clinically relevant sensorimotor changes that occur in LBP patients that improve with dry needling treatment that partially explain the physiologic mechanism of action. Published by Elsevier Ltd.

  6. Improved Survival Among all Interferon-α-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders.

    PubMed

    Cozen, Myrna L; Ryan, James C; Shen, Hui; Cheung, Ramsey; Kaplan, David E; Pocha, Christine; Brau, Norbert; Aytaman, Ayse; Schmidt, Warren N; Pedrosa, Marcos; Anand, Bhupinderjit S; Chang, Kyong-Mi; Morgan, Timothy; Monto, Alexander

    2016-06-01

    As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated. To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients. Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review. A total of 2211 patients were followed for an average of 8.5 years after enrollment. Thirty-one percent of patients received HCV antiviral therapy, 15 % with standard IFN/ribavirin only, 16 % with pegylated IFN/ribavirin, and 26.7 % of treated patients achieved sustained virologic response (SVR). Cirrhosis developed in 25.8 % of patients. Treatment nonresponders had a greater than twofold increase in the hazard of cirrhosis and hepatocellular carcinoma, compared to untreated patients, whereas SVR patients were only marginally protected from cirrhosis. Nearly 6 % developed hepatocellular carcinoma, and 27.1 % died during the follow-up period. Treated patients, regardless of response, had a significant survival benefit compared to untreated patients (HR 0.58, CI 0.46-0.72). Improved survival was also associated with college education, younger age, lower levels of alcohol consumption, and longer duration of medical service follow-up-factors typically associated with treatment eligibility. As more hepatitis C patients are now being assessed for all-oral combination therapy, these results highlight that patient compliance and limiting harmful behaviors contribute a significant proportion of the survival benefit in treated patients and that the long-term clinical benefits of SVR may be less profound than previously reported.

  7. T-Cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists.

    PubMed

    Vincent, Thierry; Portales, Pierre; Baillat, Vincent; de Boever, Corinne Merle; Le Moing, Vincent; Vidal, Michèle; Ducos, Jacques; Clot, Jacques; Reynes, Jacques; Corbeau, Pierre

    2005-03-01

    CCR5 antagonists represent promising anti-HIV agents. Yet, if the CCR5 chemokine receptor plays a positive role in hepatitis C virus (HCV) infection, CCR5 antagonists might be contraindicated in HCV/HIV-coinfected subjects. Therefore, we tested the hypothesis that the level of T-cell surface CCR5 expression, which might determine the intensity of HCV-specific T-cell recruitment into the liver, and thereby the efficiency of the anti-HCV response, could determine HCV disease evolution. For this purpose, we compared CCR5 density, measured by quantitative flow cytometry at the surface of nonactivated (human leukocyte antigen-D-related [HLA-DR]-) T cells of 51 HCV/HIV patients, with HCV load, serum aminotransferase levels, and liver histology (inflammatory activity, fibrosis, and rate of fibrosis progression). DR-CD4+ T-cell surface CCR5 density, which correlated with DR-CD8+ T-cell surface CCR5 density and was stable over time in HCV/HIV-coinfected individuals, did not correlate with any of the biologic parameters of HCV infection analyzed and was not linked to the capacity to clear the virus. In conclusion, we failed to demonstrate any impact of interindividual variability in T-cell surface CCR5 density on HCV infection, which would have argued against the use of CCR5 antagonists in HIV/HCV-coinfected subjects.

  8. The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-alpha and ribavirin combined therapy for chronic hepatitis C patients.

    PubMed

    Chen, P-J; Hwang, Y; Lin, C G-J; Wu, Y-J; Wu, L S-H

    2008-04-01

    Interferon-alpha and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-alpha and ribavirin combined therapy in patients with chronic hepatitis C.

  9. Mollicutes/HIV Coinfection and the Development of AIDS: Still Far from a Definitive Response.

    PubMed

    de Cordova, Caio Mauricio Mendes; Galgowski, Caroline; Lange, Leonardo

    2016-01-01

    Background. Mycoplasmas are known to cause various infections in humans, mainly in the respiratory and urogenital tracts. The different species are usually host-specific and cause diseases in well-defined sites. New species have been isolated, including those from HIV-infected persons. Summary. Its in vitro properties, combined with clinical findings, have led to the hypothesis that these microorganisms may act as cofactors of HIV in AIDS development. Even today this point of view is quite polemic among infectious disease specialists and many aspects remain to be clarified, in contrast to what happens, for instance, with HIV/Mycobacterium tuberculosis coinfection. Dozens of papers have been published covering aspects of Mollicutes/HIV coinfection, but they add little to no information about the putative contribution of Mollicutes to the evolution of AIDS. Very few researchers have devoted their efforts to trying to answer this question, which remains open. In this review, we discuss the evidences that may support this statement in the light of current knowledge in the field of mycoplasmology.

  10. Mollicutes/HIV Coinfection and the Development of AIDS: Still Far from a Definitive Response

    PubMed Central

    Lange, Leonardo

    2016-01-01

    Background. Mycoplasmas are known to cause various infections in humans, mainly in the respiratory and urogenital tracts. The different species are usually host-specific and cause diseases in well-defined sites. New species have been isolated, including those from HIV-infected persons. Summary. Its in vitro properties, combined with clinical findings, have led to the hypothesis that these microorganisms may act as cofactors of HIV in AIDS development. Even today this point of view is quite polemic among infectious disease specialists and many aspects remain to be clarified, in contrast to what happens, for instance, with HIV/Mycobacterium tuberculosis coinfection. Dozens of papers have been published covering aspects of Mollicutes/HIV coinfection, but they add little to no information about the putative contribution of Mollicutes to the evolution of AIDS. Very few researchers have devoted their efforts to trying to answer this question, which remains open. In this review, we discuss the evidences that may support this statement in the light of current knowledge in the field of mycoplasmology. PMID:27413383

  11. The CYP4502D6 *4 and *6 alleles are the molecular genetic markers for drug response: implications in colchicine non-responder FMF patients.

    PubMed

    Yalcıntepe, Sinem; Ozdemır, Ozturk; Sılan, Coskun; Ozen, Filiz; Uludag, Ahmet; Candan, Ferhan; Sılan, Fatma

    2016-06-01

    The cytochrome P450 2D6 (CYP2D6) is a cytochrome P450 enzyme involved in the oxidative biotransformation of the xenobiotics, carcinogens and various clinically important drugs. Patients are evaluated in three sub-groups of extensive (EM), intermediate (IM) and poor metabolizer (PM) phenotypes due to their drug-metabolising ability for the target CYP2D6 gene. Colchicine non-responsive FMF patients were prospectively genotyped for the major CYP2D6 alleles in the current study. Major CYP2D6 alleles of *1, *3, *4, *5, and *6 were genotyped for 30 responsive and 60 non-responsive FMF patients by multiplex PCR-based reverse-hybridization StripAssay and real-time PCR methods. DNA banks isolated from blood-EDTA were retrospectively used in the current patients and results were compared statistically. Increased CYP2D6 *4 and *6 allele frequencies were highly detected in the colchicine non-responsive FMF patients when compared to the responsive group. Results showed the frequencies of major CYP2D6 *1(wild), *3(2637A > delA), *4(G1934A), *5(total gene deletion) and *6(1707T del) alleles in 0.550, 0.042, 0.158, 0.025 and 0.225 for non-responder and 0.880 and 0.120 (CYP2D6*1 and *4) for the responder groups, respectively. Despite small sample size, this study suggests that there is an association between CYP2D6*4 and CYP2D6*6 alleles and drug intoxicants in colchicine non-responder FMF patients.

  12. Beneficial Metabolic Effects of Duodenal Jejunal Bypass Liner for the Treatment of Adipose Patients with Type 2 Diabetes Mellitus: Analysis of Responders and Non-Responders.

    PubMed

    Stratmann, B; Krepak, Y; Schiffer, E; Jarick, I; Hauber, M; Lee-Barkey, Y H; Fischer, M; Tschoepe, D

    2016-09-01

    Implantation of a duodenal-jejunal endoluminal bypass liner (DJBL) has shown to induce weight loss and to improve metabolic parameters. DJBL is a reversible endoduodenal sleeve mimicking duodenal bypass while lacking risks and limitations of bariatric surgery.Effects on metabolic control, body mass parameters, appetite regulation, glucose tolerance, organ health, and lipid profile were determined in 16 morbidly overweight patients with type 2 diabetes mellitus. In addition, relevant hormones (leptin, ghrelin, gastric inhibitory peptide, glucagon-like peptide, and insulin) were measured by enzyme-linked immunosorbent assay (ELISA) and chemiluminescent microparticle immunoassay (CMIA) at 0, 1, 32, and 52 weeks post-implant following a mixed meal tolerance test. Lipoprotein subclasses were analysed by proton nuclear magnetic resonance ((1)H NMR) spectrometry. DJBL provoked weight loss, a decrease in fat mass, and an improvement in insulin resistance and hepatic function in most but not all of the patients, but in the long term did not increase gut hormone fasting levels pointing to a combined effect of more than gut parameters alone. Lipidome analysis was done in 10 patients, allowing classification to responders and non-responders by reduction of sLDL-p subfraction; and to further analyse the atherogenic profile. Responders showed an overall more pronounced effect regarding improvement of HbA1c, BMI, and HOMA index.Implantation of a DJBL in obese type 2 diabetes patients does not per se lead to an improvement of the metabolic situation. Further analyses including larger cohorts have to be performed to identify responding patients, to better treat non-responders and to analyse the key effectors. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients.

    PubMed

    Milanesi, Elena; Hadar, Adva; Maffioletti, Elisabetta; Werner, Haim; Shomron, Noam; Gennarelli, Massimo; Schulze, Thomas G; Costa, Marta; Del Zompo, Maria; Squassina, Alessio; Gurwitz, David

    2015-07-01

    Bipolar disorder (BD) is a chronic psychiatric illness with an unknown etiology. Lithium is considered the cornerstone in the management of BD, though about 50-60 % of patients do not respond sufficiently to chronic treatment. Insulin-like growth factor 1 (IGF1) has been identified as a candidate gene for BD susceptibility, and its low expression has been suggested as a putative biomarker for lithium unresponsiveness. In this study, we examined the in vitro effects of insulin-like growth factor 1 (IGF-1) on lithium sensitivity in lymphoblastoid cell lines (LCLs) from lithium responder (R) and non-responder (NR) bipolar patients. Moreover, we evaluated levels of microRNA let-7c, a small RNA predicted to target IGF1. We found that exogenous IGF-1 added to serum-free media increased lithium sensitivity selectively in LCLs from NR BD patients. However, no significant differences were observed when comparing let-7c expression in LCLs from R vs. NR BD patients. Our data support a key role for IGF-1 in lithium resistance/response in the treatment of bipolar disorder.

  14. The value of time-intensity curves obtained after microbubble contrast agent injection to discriminate responders from non-responders to anti-inflammatory medication among patients with Crohn's disease.

    PubMed

    Quaia, Emilio; Cabibbo, Biagio; De Paoli, Luca; Toscano, William; Poillucci, Gabriele; Cova, Maria Assunta

    2013-06-01

    To assess the value of time-intensity curves obtained after sulphur hefluoride-filled microbubble contrast agent injection to discriminate responders from non-responders among patients with Crohn's disease (CD). Forty-three patients (29 male and 14 female; mean age ± SD, 48.5 ± 17.17 years) with initial diagnosis of active CD were recruited. In each patient, the therapeutic outcome was assessed after 12 weeks from the beginning of pharmacologic treatment. The terminal ileal loop was scanned after sulphur hexafluoride-filled microbubble injection, and the digital cine-clip registered during the first-pass dynamic enhancement was quantified in gray-scale levels. The percentage of maximal enhancement, time to peak enhancement, and area under the time-intensity curve in responders vs. non-responders were compared by Mann-Whitney U non-parametric test. Responders (n = 25 patients) vs. non-responders (n = 18) differed in the area under the time-intensity curve (621.58 ± 374.53 vs. 1,199.64 ± 386.39 P < 0.05), while they did not differ in percentage of maximal enhancement (41.26 ± 15.22 vs. 43.17 ± 4.41, P = 0.25) and time to peak enhancement (11.31 ± 3.06 vs. 10.12 ± 3.47, P = 0.15). The area under the time-intensity curve obtained after microbubble injection was the only parameter to discriminate responders from non-responders among patients with CD during pharmacologic treatment. • Dynamic ultrasound using microbubble contrast agents can help assess inflammatory bowel disease • Time-intensity curves can assess therapeutic outcome in Crohn's disease (CD) • The area under the time-intensity curve differentiates responders from non-responders during pharmacological treatment.

  15. Fesoterodine for the Treatment of Nocturnal Urgency in Patients with Overactive Bladder Syndrome: An Analysis of Responders and Nonresponders.

    PubMed

    Khusid, Johnathan A; Weiss, Jeffrey P; Carlsson, Martin O; Mangan, Erin K

    2017-05-04

    A recent study demonstrated improvement in nocturnal urgency in patients with overactive bladder when treated with fesoterodine. In the current study we aimed to determine which bladder diary parameters predict the response to fesoterodine in these patients. Patients with nocturnal urgency completed a 2-week, single-blind placebo run in followed by 1:1 double-blind randomization to 12 weeks of fesoterodine or placebo. We analyzed bladder diary parameter changes from baseline to week 12, including the actual number of night voids (total number of nocturia episodes), maximum voided volume, nocturnal bladder capacity, Nocturnal Bladder Capacity Index (NBCi) (actual number of night voids - nocturnal urine volume/maximum voided volume - 1), nocturnal urine volume, the nocturia index (nocturnal urine volume/maximum voided volume) and the nocturnal polyuria index (nocturnal urine volume/24-hour volume). Additionally, we analyzed OAB-q (Overactive Bladder Questionnaire) changes. There was a linear relationship between the likelihood of being a responder for NBCi and the nocturia index. Responders had a significant decrease in nocturnal urine volume relative to baseline (-181.7 ml, p <0.01). Neither group showed a significant change in maximum voided volume relative to baseline. There was a significant decrease in NBCi and the nocturia index in responders (-0.82 and -0.61, respectively, each p <0.01). Responders demonstrated improvement in the OAB-q concern, coping, sleep, bother and total score metrics. Patients with nocturnal urgency secondary to overactive bladder syndrome and low nocturnal bladder capacity with a mismatch between nocturnal urine production and bladder capacity may benefit from fesoterodine. Symptom improvement appears to be mediated by increases in typical rather than maximum nocturnal voided volumes. Symptom improvement was associated with improved quality of life. Copyright © 2017 American Urological Association Education and Research, Inc. Published

  16. St. John's Wort in patients non-responders to clopidogrel undergoing percutaneous coronary intervention: a single-center randomized open-label trial (St. John's Trial).

    PubMed

    Trana, Catalina; Toth, Gabor; Wijns, William; Barbato, Emanuele

    2013-06-01

    We assessed if St. John's Wort (SJW) improves platelet response in patients (pts) resistant to clopidogrel after percutaneous coronary intervention (PCI). Stable angina pts non-responders to 600 mg clopidogrel (P2Y12 reaction units (PRU) >240) were randomized (2:1) to SJW (n = 15) or placebo (n = 8). SJW (300 mg × 3/day) was administrated for 2 weeks after PCI. Platelet reactivity was assessed by VerifyNowTM before (BL), 2 (T1), and 4 weeks (T2) after PCI. PRU significantly changed during protocol in SJW (BL (316 ± 60) vs. T1 (170 ± 87) vs. T2 (220 ± 96), p < 0.0001) and placebo group (BL (288 ± 36) vs. T1 (236 ± 31) vs. T2 (236 ± 62), p = 0.046). Yet, PRU changes from BL were higher at T1 in SJW than in placebo group (Δ%, -47 ± 24 vs. -16 ± 15, p = 0.0033), with no differences at T2 between the groups (Δ%, -30 ± 29 vs. -17 ± 24, p = 0.30). Residual platelet reactivity improved with SJW during the first month post-PCI.

  17. Real-world effectiveness of natalizumab and fingolimod compared with self-injectable drugs in non-responders and in treatment-naïve patients with multiple sclerosis.

    PubMed

    Prosperini, Luca; Saccà, Francesco; Cordioli, Cinzia; Cortese, Antonio; Buttari, Fabio; Pontecorvo, Simona; Bianco, Assunta; Ruggieri, Serena; Haggiag, Shalom; Brescia Morra, Vincenzo; Capra, Ruggero; Centonze, Diego; Di Battista, Giancarlo; Ferraro, Elisabetta; Francia, Ada; Galgani, Simonetta; Gasperini, Claudio; Millefiorini, Enrico; Mirabella, Massimiliano; Pozzilli, Carlo

    2017-02-01

    In this independent, multicentre post-marketing study we directly compared the effectiveness of natalizumab (NTZ), fingolimod (FNG) and self-injectable drugs (INJ), in non-responders to first immunomodulating treatment and in highly active treatment-naïve patients with multiple sclerosis. As main outcome measure we considered the proportions of patients with no evidence of disease activity (NEDA-3), defined as absence of relapses, disability worsening and radiological activity. A total of 567 non-responders to interferon beta (IFNB) or glatiramer acetate (GA) [dataset A] and 216 highly active treatment-naïves [dataset B] were followed up to 24 months from the beginning of NTZ, FNG or INJ, i.e. switching from IFNB to GA or viceversa (in the case of non-responders) or starting high-dose IFNB (in the case of highly active treatment-naïves). Propensity score matching in a 1:1:1 ratio was used to select only patients with similar baseline characteristics, retaining 330 and 120 patients in dataset A and B, respectively. In dataset A, the 24-month proportion with NEDA-3 was greater in both NTZ group (67%) and FNG group (42%) than in INJ group (35%) (p ≤ 0.016); however, NTZ was superior to FNG in promoting the attainment of NEDA-3 status (p = 0.034). In dataset B, the 24-month proportion with NEDA-3 was greater in NTZ group (75%) and FNG group (67%) than in INJ group (40%), but the small cohort sizes most likely prevented the detection of any statistically significant difference. Our study provides real-world evidence that NTZ was more effective than both FNG and INJ in non-responders, while it could seem that, in highly active treatment-naïves, NTZ was as effective as FNG and both were superior to INJ.

  18. Time-Intensity Curves Obtained after Microbubble Injection Can Be Used to Differentiate Responders from Nonresponders among Patients with Clinically Active Crohn Disease after 6 Weeks of Pharmacologic Treatment.

    PubMed

    Quaia, Emilio; Sozzi, Michele; Angileri, Roberta; Gennari, Antonio Giulio; Cova, Maria Assunta

    2016-11-01

    Purpose To assess whether contrast material-enhanced ultrasonography (US) can be used to differentiate responders from nonresponders among patients with clinically active Crohn disease after 6 weeks of pharmacologic treatment. Materials and Methods This prospective study was approved by our ethics committee, and written informed consent was obtained from all patients. Fifty consecutive patients (26 men and 24 women; mean age, 34.76 years ± 9) with a proved diagnosis of active Crohn disease who were scheduled to begin therapy with biologics (infliximab or adalimumab) were included, with enrollment from June 1, 2013, to June 1, 2015. In each patient, the terminal ileal loop was imaged with contrast-enhanced US before the beginning and at the end of week 6 of pharmacologic treatment. Time-intensity curves obtained in responders (those with a decrease in the Crohn disease endoscopic index of severity score of 25-44 before treatment to 10-15 after treatment, an inflammatory score <7, and/or a decrease ≥70 in the Crohn disease activity index score compared with baseline) and nonresponders were compared with Mann-Whitney test. Results Responders (n = 31) and nonresponders (n = 19) differed (P < .05) in the percent change of peak enhancement (-40.78 ± 62.85 vs 53.21 ± 72.5; P = .0001), wash-in (-34.8 ± 67.72 vs 89.44 ± 145.32; P = .001) and washout (-5.64 ± 130.71 vs 166.83 ± 204.44; P = .002) rate, wash-in perfusion index (-42.29 ± 59.21 vs 50.96 ± 71.13; P = .001), area under the time-intensity curve (AUC; -46.17 ± 48.42 vs 41.78 ± 87.64; P = .001), AUC during wash-in (-43.93 ± 54.29 vs 39.79 ± 70.85; P = .001), and AUC during washout (-49.36 ± 47.42 vs 42.65 ± 97.09; P = .001). Responders and nonresponders did not differ in the percent change of rise time (5.09 ± 49.13 vs 6.24 ± 48.06; P = .93) and time to peak enhancement (8.82 ± 54.5 vs 10.21 ± 43.25; P = .3). Conclusion Analysis of time-intensity curves obtained after injection of microbubble

  19. The Proton Pump Inhibitor Non-Responder: A Clinical Conundrum

    PubMed Central

    Hussain, Zilla H; Henderson, Emily E; Maradey-Romerao, Carla; George, Nina; Fass, Ronnie; Lacy, Brian E

    2015-01-01

    Gastroesophageal reflux disease (GERD) is a highly prevalent chronic condition where in stomach contents reflux into the esophagus causing symptoms, esophageal injury, and subsequent complications. Proton pump inhibitors (PPI) remain the mainstay of therapy for acid suppression. Despite their efficacy, significant proportions of GERD patients are either partial or non-responders to PPI therapy. Patients should be assessed for mechanisms that can lead to PPI failure and may require further evaluation to investigate for alternative causes. This monograph will outline a diagnostic approach to the PPI non-responder, review mechanisms associated with PPI failure, and discuss therapeutic options for those who fail to respond to PPI therapy. PMID:26270485

  20. A population-based record linkage study of mortality in hepatitis C-diagnosed persons with or without HIV coinfection in Scotland.

    PubMed

    McDonald, Scott A; Hutchinson, Sharon J; Bird, Sheila M; Mills, Peter R; Dillon, John; Bloor, Mick; Robertson, Chris; Donaghy, Martin; Hayes, Peter; Graham, Lesley; Goldberg, David J

    2009-06-01

    Infection with the hepatitis C virus (HCV) is known to increase the risk of death from severe liver disease and, because HCV status is strongly associated with a history of injecting drug use, the effect of a key disease progression cofactor, infection with human immunodeficiency virus (HIV), is of interest. We examined all-cause, liver-related and drug-related mortality and excess risk of death from these causes in a large cohort of HCV-monoinfected and HIV-coinfected persons in Scotland. The study population consisted of 20,163 persons confirmed to be infected with hepatitis C through laboratory testing in Scotland between 1991 and 2005. Records with sufficient identifiers were linked to the General Register Office for Scotland death register to retrieve associated mortality data, and were further linked to a national database of HIV-positive individuals to determine coinfection status. A total of 1715 HCV monoinfected and 305 HIV coinfected persons died of any cause during the follow-up period (mean of 5.4 and 6.4 years, respectively). Significant excess mortality was observed in both HCV monoinfected and HIV coinfected populations from liver-related underlying causes (standardised mortality ratios of 25, 95% CI = 23-27; and 37, 95% CI = 26-52 for the two groups, respectively) and drug-related causes (25, 95% CI = 23-27; 39, 95% CI = 28-53. The risk of death from hepatocellular carcinoma, alcoholic or non-alcoholic liver disease, or from a drug-related cause, was greatly increased compared with the general Scottish population, with the highest standardised mortality ratio observed for hepatocellular carcinoma in the monoinfected group (70, 95% CI = 57-85). This study has revealed considerable excess mortality from liver- and drug-related causes in the Scottish HCV-diagnosed population; these data are crucial to inform on the clinical management, and projected future public health burden, of HCV infection.

  1. Non-pathological infection of macaques by an attenuated mycobacterial vaccine is not reactivated in the setting of HIV coinfection.

    PubMed

    Foreman, Taylor Wayne; Veatch, Ashley Victoria; LoBato, Denae Nadine; Didier, Peter John; Doyle-Meyers, Lara Angela; Russell-Lodrigue, Kasi Elizabeth; Lackner, Andrew Alan; Kousoulas, Konstantin Gus; Khader, Shabaana Abdul; Kaushal, Deepak; Mehra, Smriti

    2017-09-18

    Failure to replace BCG with efficacious anti-TB vaccines have prompted out-of-the-box thinking, including pulmonary vaccination in order to elicit local immunity. MtbΔsigH, a stress-response attenuated strain, protected against lethal TB when used to vaccinate macaques via inhalation. While live mycobacterial vaccines show promising efficacy, HIV co-infection and the resulting immunodeficiency prompts safety concerns about their use. We assessed the persistence and safety of MtbΔsigH, delivered directly to the lungs, in the setting of HIV coinfection. Macaques were aerosol vaccinated with ΔsigH and subsequently challenged with SIVmac239. BAL and tissues were sampled for mycobacterial persistence, pathology and immune correlates. Only 35% and 3.5% lung samples were positive for live-bacilli and granulomas, respectively. Our results therefore suggest that the non-pathological infection of macaque lungs by ΔsigH was not reactivated by SIV, despite high viral titers and massive ablation of pulmonary CD4(+) T-cells. Protective pulmonary responses were retained, including vaccine-induced bronchus associated lymphoid tissue (iBALT) and CD8(+) effector memory cells. Despite acute SIV infection, all animals remained asymptomatic of pulmonary TB. These findings highlight the efficacy of mucosal vaccination of this attenuated strain and will guide its further development to potentially combat TB in HIV endemic areas. Our results also suggest that lack of pulmonary pathology is a key correlate of safety for live mycobacterial vaccines. Copyright © 2017. Published by Elsevier Inc.

  2. A nationwide population-based cross-sectional survey of health-related quality of life in patients with myeloproliferative neoplasms in Denmark (MPNhealthSurvey): survey design and characteristics of respondents and nonrespondents

    PubMed Central

    Brochmann, Nana; Flachs, Esben Meulengracht; Christensen, Anne Illemann; Andersen, Christen Lykkegaard; Juel, Knud; Hasselbalch, Hans Carl; Zwisler, Ann-Dorthe

    2017-01-01

    Objective The Department of Hematology, Zealand University Hospital, Denmark, and the National Institute of Public Health, University of Southern Denmark, created the first nationwide, population-based, and the most comprehensive cross-sectional health-related quality of life (HRQoL) survey of patients with myeloproliferative neoplasms (MPNs). In Denmark, all MPN patients are treated in public hospitals and treatments received are free of charge for these patients. Therefore, MPN patients receive the best available treatment to the extent of its suitability for them and if they wish to receive the treatment. The aims of this article are to describe the survey design and the characteristics of respondents and nonrespondents. Material and methods Individuals with MPN diagnoses registered in the Danish National Patient Register (NPR) were invited to participate. The registers of the Danish Civil Registration System and Statistics Denmark provided information regarding demographics. The survey contained 120 questions: validated patient-reported outcome (PRO) questionnaires and additional questions addressing lifestyle. Results A total of 4,704 individuals were registered with MPN diagnoses in the NPR of whom 4,236 were eligible for participation and 2,613 (62%) responded. Overall, the respondents covered the broad spectrum of MPN patients, but patients 70–79 years old, living with someone, of a Danish/Western ethnicity, and with a higher level of education exhibited the highest response rate. Conclusion A nationwide, population-based, and comprehensive HRQoL survey of MPN patients in Denmark was undertaken (MPNhealthSurvey). We believe that the respondents broadly represent the MPN population in Denmark. However, the differences between respondents and nonrespondents have to be taken into consideration when examining PROs from the respondents. The results of the investigation of the respondents’ HRQoL in this survey will follow in future articles. PMID:28280390

  3. Natural history and treatment of HCV/HIV coinfection: Is it time to change paradigms?

    PubMed

    Arends, Joop E; Lieveld, Faydra I; Boeijen, Lauke L; de Kanter, Clara T M M; van Erpecum, Karel J; Salmon, Dominique; Hoepelman, Andy I M; Asselah, Tarik; Ustianowski, Andrew

    2015-11-01

    Evidence over the past decades have shown that HIV/HCV coinfected patients did not respond as well to HCV therapy as HCV mono-infected patients. However, these paradigms are being recently reassessed with the improvements of care for HIV and HCV patients. This article reviews these original paradigms and how the new data is impacting upon them. Treatment efficacy now appears comparable for HIV/HCV coinfected and HCV mono-infected patients, while liver fibrosis progression is increasingly similar in optimally managed patients. Additional importance of therapy is directed to drug-drug interactions and the impact of HCV reinfection, as well as the possibility of transmitted drug resistance.

  4. [Hepatitis C treatment in special patient groups].

    PubMed

    Berenguer, Marina; Jorquera, Francisco; Ángel Serra, Miguel; Sola, Ricard; Castellano, Gregorio

    2014-07-01

    The treatment plan for chronic hepatitis C in special populations varies according to comorbidity and the current evidence on treatment. In patients with hepatitis C virus and HIV coinfection, the results of dual therapy (pegylated interferon plus ribavirin) are poor. In patients with genotype 1 infection, triple therapy (dual therapy plus boceprevir or telaprevir) has doubled the response rate, but protease inhibitors can interact with some antiretroviral drugs and provoke more adverse effects. These disadvantages are avoided by the new, second-generation, direct-acting antiviral agents. In patients who are candidates for liver transplantation or are already liver transplant recipients, the optimal therapeutic option at present is to combine the new antiviral agents, with or without ribavirin and without interferon. The treatment of patients under hemodialysis due to chronic renal disease continues to be dual therapy (often with reduced doses of pegylated interferon and ribavirin), since there is still insufficient information on triple therapy and the new antiviral agents. In mixed cryoglobulinemia, despite the scarcity of experience, triple therapy seems to be superior to dual therapy and may be used as rescue therapy in non-responders to dual therapy. However, a decision must always be made on whether antiviral treatment should be used concomitantly or after immunosuppressive therapy. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  5. Fatal Pediatric Cerebral Malaria Is Associated with Intravascular Monocytes and Platelets That Are Increased with HIV Coinfection.

    PubMed

    Hochman, Sarah E; Madaline, Theresa F; Wassmer, Samuel C; Mbale, Emmie; Choi, Namjong; Seydel, Karl B; Whitten, Richard O; Varughese, Julie; Grau, Georges E R; Kamiza, Steve; Molyneux, Malcolm E; Taylor, Terrie E; Lee, Sunhee; Milner, Danny A; Kim, Kami

    2015-09-22

    Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%, P < 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%, P = 0.0178, chi-square test). HIV-infected (HIV(+)) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months, P = 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV(+) and HIV-uninfected children with fatal CM. Children with autopsy-confirmed CM had significantly (>9 times) more accumulations of intravascular monocytes and platelets, but not neutrophils, than did children with nonmalarial causes of coma. The monocyte and platelet accumulations were significantly (>2-fold) greater in HIV(+) children than in HIV-uninfected children with autopsy-confirmed CM. Our findings indicate that HIV is a risk factor for CM and for death from CM, independent of traditional measures of HIV disease severity. Brain histopathology supports the hypotheses that inflammation and coagulation contribute to the pathogenesis of pediatric CM and that immune dysregulation in HIV(+) children exacerbates the pathological features associated with CM. IMPORTANCE : There are nearly 1 million malaria deaths yearly, primarily in sub-Saharan African children. Cerebral malaria (CM), marked by coma and sequestered malaria parasites in brain blood vessels, causes half of these deaths, although the mechanisms causing

  6. Fatal Pediatric Cerebral Malaria Is Associated with Intravascular Monocytes and Platelets That Are Increased with HIV Coinfection

    PubMed Central

    Hochman, Sarah E.; Madaline, Theresa F.; Wassmer, Samuel C.; Mbale, Emmie; Choi, Namjong; Seydel, Karl B.; Whitten, Richard O.; Varughese, Julie; Grau, Georges E. R.; Kamiza, Steve; Molyneux, Malcolm E.; Taylor, Terrie E.; Lee, Sunhee; Milner, Danny A.

    2015-01-01

    ABSTRACT  Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%, P < 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%, P = 0.0178, chi-square test). HIV-infected (HIV+) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months, P = 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV+ and HIV-uninfected children with fatal CM. Children with autopsy-confirmed CM had significantly (>9 times) more accumulations of intravascular monocytes and platelets, but not neutrophils, than did children with nonmalarial causes of coma. The monocyte and platelet accumulations were significantly (>2-fold) greater in HIV+ children than in HIV-uninfected children with autopsy-confirmed CM. Our findings indicate that HIV is a risk factor for CM and for death from CM, independent of traditional measures of HIV disease severity. Brain histopathology supports the hypotheses that inflammation and coagulation contribute to the pathogenesis of pediatric CM and that immune dysregulation in HIV+ children exacerbates the pathological features associated with CM. Importance  There are nearly 1 million malaria deaths yearly, primarily in sub-Saharan African children. Cerebral malaria (CM), marked by coma and sequestered malaria parasites in brain blood vessels, causes half of these deaths, although the mechanisms

  7. Low Efficacy of Pegylated Interferon plus Ribavirin plus Nitazoxanide for HCV Genotype 4 and HIV Coinfection

    PubMed Central

    Macías, Juan; López-Cortés, Luis F.; Téllez, Francisco; Recio, Eva; Ojeda-Burgos, Guillermo; Ríos, MªJosé; Rivero-Juárez, Antonio; Delgado, Marcial; Jeremías, Rivas-; Pineda, Juan A.

    2015-01-01

    Background Nitazoxanide (NTZ) plus pegylated interferon and ribavirin (Peg-IFN/RBV) improved the sustained virological response (SVR) achieved with Peg-IFN/RBV in hepatitis C virus genotype 4 (HCV-4)-monoinfected patients. There are no data currently on the efficacy of Peg-IFN/RBV plus NTZ for human immunodeficiency virus (HIV)/HCV-4 coinfection. Therefore, the objectives of this clinical trial were to assess the efficacy and to evaluate the safety of Peg-IFN/RBV plus NTZ in HIV/HCV-4-coinfected patients. Patients and Methods This was an open-label, single arm, multicenter phase II pilot clinical trial (NCT01529073) enrolling HIV-infected individuals with HCV-4 chronic infection, naïve to HCV therapy. Patients were treated with NTZ 500 mg bid for 4 weeks, followed by NTZ 500 mg bid plus Peg-IFN alpha-2b 1.5 μg/kg/week plus weight-adjusted RBV during 48 weeks. Analyses were done by intention-to-treat (ITT, missing = failure). A historical cohort of HIV/HCV-4-infected patients treated with Peg-IFN alpha-2b and RBV at the same area was used as control. Results Two (9.5%) of 21 patients included in the trial compared with 5 (21.7%) of 23 patients included in the historical cohort achieved SVR (SVR risk difference, -12.2%; 95% confidence interval, -33.2% to 8.8%; p = 0.416). Virological failure was due to lack of response in 13 (62%) individuals recruited in the trial. Two (9.5%) patients included in the trial and two (9.5%) individuals from the historical cohort discontinued permanently due to adverse events. Conclusions No increase in SVR was observed among HIV/HCV-4-coinfected patients receiving Peg-IFN/RBV plus NTZ compared with a historical cohort treated with Peg-IFN/RBV. Interruptions due to adverse events of Peg-IFN/RBV plus NTZ were similar to those of dual therapy. Trial Registration ClinicalTrials.gov NCT01529073 PMID:26640956

  8. Absence of neurocognitive effect of hepatitis C infection in HIV-coinfected people

    PubMed Central

    Vaida, Florin; Kao, Yu-Ting; Franklin, Donald R.; Letendre, Scott L.; Collier, Ann C.; Marra, Christina M.; Gelman, Benjamin B.; McArthur, Justin C.; Morgello, Susan; Simpson, David M.; Grant, Igor; Heaton, Robert K.

    2015-01-01

    Objective: To investigate the effect of hepatitis C virus (HCV) on neurocognitive performance in chronically HIV-infected patients enrolled in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study. Methods: A total of 1,582 participants in CHARTER who were tested for HCV antibody underwent neurocognitive testing; serum HCV RNA was available for 346 seropositive patients. Neurocognitive performance was compared in 408 HCV-seropositive and 1,174 HCV-seronegative participants and in a subset of 160 seropositive and 707 seronegative participants without serious comorbid neurologic conditions that might impair neurocognitive performance, using linear regression and taking into account HIV-associated and demographic factors (including IV drug use) and liver function. Results: Neurocognitive performance characterized by global deficit scores and the proportion of individuals who were impaired were the same in the HCV-seropositive and HCV-seronegative groups. In univariable analyses in the entire sample, only verbal domain scores showed small statistically different superior performance in the HCV+ group that was not evident in multivariable analysis. In the subgroup without significant comorbidities, scores in all 7 domains of neurocognitive functioning did not differ by HCV serostatus. Among the HCV-seropositive participants, there was no association between neurocognitive performance and serum HCV RNA concentration. Conclusion: In HIV-infected patients, HCV coinfection does not contribute to neurocognitive impairment, at least in the absence of substantial HCV-associated liver damage, which was not evident in our cohort. PMID:25503616

  9. Text messaging to decrease tuberculosis treatment attrition in TB-HIV coinfection in Uganda.

    PubMed

    Hermans, Sabine M; Elbireer, Sawsan; Tibakabikoba, Harriet; Hoefman, Bas J; Manabe, Yukari C

    2017-01-01

    Low tuberculosis (TB) treatment completion rates in sub-Saharan Africa are an important driver of multidrug resistance. Mobile technology-based interventions have been shown to improve adherence to antiretroviral therapy in sub-Saharan Africa. We aimed to test the effect of a short-message service (SMS) intervention on loss to follow-up (LFU). In this quasi-experimental study, all adult, literate, HIV-infected patients with mobile phone access diagnosed with TB between November 2010 and October 2011 in an urban clinic in Uganda were eligible to receive adherence and appointment reminders and educational quizzes during the first 8 weeks of TB treatment. Their risk of LFU in the first 8 weeks of treatment was compared with that of patients starting treatment between March 2009 and August 2010 using logistic regression. One of 183 (0.5%) enrolled patients was lost to FU during the intervention compared to six of 302 (2.0%) in the preintervention control group (RR 0.27, 95% CI 0.03-2.07; P=0.22). The SMS intervention was rated as very helpful by 96%. Barriers identified included interrupted phone access (26%, median 14 days) and difficulties responding by SMS. The response rate to educational quizzes was below 10%. There were no unintentional disclosures of TB or HIV status due to the intervention. An SMS reminder service did not show a clear effect on short-term risk of LFU in this study, which was underpowered due to a lower baseline risk in the control group than expected. The SMS-reminder service was rated highly, and there were no breaches of confidentiality. Important technological barriers have implications for larger-scale implementation, not only for TB but also other disease modalities.

  10. Bridging intravenous-intra-arterial rescue strategy increases recanalization and the likelihood of a good outcome in nonresponder intravenous tissue plasminogen activator-treated patients: a case-control study.

    PubMed

    Rubiera, Marta; Ribo, Marc; Pagola, Jorge; Coscojuela, Pilar; Rodriguez-Luna, David; Maisterra, Olga; Ibarra, Bernardo; Piñeiro, Socorro; Meler, Pilar; Romero, Francisco J; Alvarez-Sabin, Jose; Molina, Carlos A

    2011-04-01

    Safety and efficacy of the "bridging therapy" (intra-arterial [IA] reperfusion rescue for nonresponder intravenous [IV] tissue plasminogen activator [tPA]-treated patients) is a matter of debate. Our aim was to compare IV and IV-IA thrombolysis using a case-control approach. Consecutive patients with proximal intracranial occlusion who received IA reperfusion procedures after unsuccessful IV tPA (lack of clinical improvement and arterial recanalization 1 hour after tPA bolus) were studied (IV-IA group). They were compared with occluded vessel, clot location, stroke severity, and time to treatment-matched 1 to 2 historical patients from our prospective IV tPA database with persistent occlusion 1 hour after IV tPA (IV-NR group). Arterial occlusion and recanalization were assessed with transcranial Doppler. Clinical evaluation was assessed by National Institutes of Health Stroke Scale at baseline, 24 hours, and at discharge. Symptomatic intracranial hemorrhage was defined according to the National Institute of Neurological Disorders and Stroke trial. Functional evaluation was determined by modified Rankin Scale, being functional independency defined by modified Rankin Scale score ≤2. Forty-two IV-IA patients were compared with 84 matched IV-NR. Mean age was 71.5±2.9 years, 58 (46%) were women, and baseline median National Institutes of Health Stroke Scale score was 20 (interquartile range, 5). Mean time from symptoms to IV tPA was 176.9±113 minutes. On transcranial Doppler, complete recanalization was significantly higher in IV-IA than control subjects (12 hours: 45.2% versus 18.1%, P=0.002; 24 hours: 46.3% versus 25.3%, P=0.016) with nonsignificant better clinical evolution at 24 hours (40.5% versus 30.1%, P=0.169) and discharge (52.5% versus 39.5%, P=0.123). Symptomatic intracranial hemorrhage was similar (IV-IA 11.9% versus IV-NR 6%, P=0.205). Mortality at 3 months was 50% in the IV-IA group and 35.8% in the IV-NR (P=0.154). Forty percent of IV-IA patients were

  11. Abatacept (cytotoxic T lymphocyte antigen 4-immunoglobulin) improves B cell function and regulatory T cell inhibitory capacity in rheumatoid arthritis patients non-responding to anti-tumour necrosis factor-α agents.

    PubMed

    Picchianti Diamanti, A; Rosado, M M; Scarsella, M; Germano, V; Giorda, E; Cascioli, S; Laganà, B; D'Amelio, R; Carsetti, R

    2014-09-01

    The use of biological agents combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients has strongly improved disease outcome. In this study, the effects of abatacept on the size and function of circulating B and T cells in RA patients not responding to anti-tumour necrosis factor (TNF)-α have been analysed, with the aim of identifying immunological parameters helpful to choosing suitable tailored therapies. We analysed the frequency of peripheral B and T cell subsets, B cell function and T regulatory cell (Treg ) inhibitory function in 20 moderate/severe RA patients, according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, primary non-responders to one TNF-α blocking agent, who received abatacept + MTX. Patients were studied before and 6 months after therapy. We found that abatacept therapy significantly reduced disease activity score on 44 joints (DAS)/erythrocyte sedimentation rate (ESR) values without causing severe side effects. The size of the circulating B and T cell compartments in RA patients was not significantly different from healthy donors, but B cell proliferation and plasma cell differentiation was impaired before therapy and restored by abatacept. While Treg cell frequency was normal, its inhibitory function was absent before therapy and was partially recovered 6 months after abatacept. B and Treg cell function is impaired in RA patients not responding to the first anti-TNF-α agent. Abatacept therapy was able to rescue immune function and led to an effective and safe clinical outcome, suggesting that RA patients, in whom anti-TNF-α failed, are immunologically prone to benefit from an agent targeting a different pathway.

  12. Pharmacokinetic interactions between telaprevir and antiretroviral drugs in HIV/HCV-coinfected patients with advanced liver fibrosis and prior HCV non-responders.

    PubMed

    Milazzo, Laura; Cattaneo, Dario; Calvi, Elisa; Gervasoni, Cristina; Mazzali, Cristina; Ronzi, Paola; Peri, Anna Maria; Ridolfo, Anna Lisa; D'Avolio, Antonio; Antinori, Spinello

    2015-05-01

    Complex drug-drug interactions have been reported with concurrent administration of telaprevir (TVR) and human immunodeficiency virus (HIV) protease inhibitors (PIs), leading to relevant limitations of the therapeutic options for patients coinfected with hepatitis C virus (HCV) and HIV. However, little is known about the pharmacokinetics and drug interactions between TVR and antiretrovirals in HIV/HCV-coinfected patients with advanced liver fibrosis. Here we report the pharmacokinetics of TVR and antiretrovirals in a cohort of HIV/HCV genotype 1-coinfected patients with advanced liver fibrosis treated with TVR-based triple anti-HCV therapy. No significant differences were observed in the pharmacokinetics of atazanavir, amprenavir or tenofovir at baseline and at Day 15 of TVR, whereas the AUC0-4h of darunavir was 36% lower in the presence of TVR (AUC0-4h 15007ngh/mL and 9563ngh/mL at baseline and at Day 15 of TVR administration, respectively). Noteworthy, the AUC0-4h, Cmin and Cmax of raltegravir were reduced by 61%, 50% and 64%, respectively. However, none of the patient's plasma levels of tenofovir, atazanavir, amprenavir or raltegravir declined below their minimum effective concentrations even in association with TVR, and no HIV treatment failure occurred. A non-significant trend for lower TVR exposure was seen in patients concomitantly given amprenavir versus those given atazanavir (AUC0-4h, 9840ngh/mL and 13345ngh/mL, respectively). In conclusion, this study highlighted the feasibility of maintaining the current antiretroviral regimen in HIV/HCV-coinfected patients, even when significant interactions with TVR are predictable, whenever a change of HIV PIs is not deemed appropriate.

  13. Intradermal versus intramuscular hepatitis B vaccination in hemodialysis patients: a prospective open-label randomized controlled trial in nonresponders to primary vaccination.

    PubMed

    Barraclough, Katherine A; Wiggins, Kathryn J; Hawley, Carmel M; van Eps, Carolyn L; Mudge, David W; Johnson, David W; Whitby, Michael; Carpenter, Sally; Playford, E Geoffrey

    2009-07-01

    Primary hepatitis B virus (HBV) vaccination through the intramuscular (IM) route is less efficacious in dialysis patients than in the general population. Previous studies suggest improved seroconversion with intradermal (ID) vaccination. Prospective open-label randomized controlled trial. Hemodialysis patients nonresponsive to primary HBV vaccination. Revaccination with either ID (10 microg of vaccine every week for 8 weeks) [DOSAGE ERROR CORRECTED] or IM (40 microg of vaccine at weeks 1 and 8) HBV vaccine . proportion of patients achieving HBV surface antibody (anti-HBs) titer of 10 IU/L or greater within 2 months of vaccination course. time to seroconversion, predictors of seroconversion, peak antibody titer, duration of seroprotection, and safety and tolerability of vaccine. Anti-HBs titer to 24 months. 59 patients were analyzed. Seroconversion rates were 79% ID versus 40% IM (P = 0.002). The unadjusted odds ratio for seroconversion for ID versus IM was 5.5 (95% confidence interval [CI], 1.6 to 18.4) and increased with adjustment for baseline differences. The only factor predictive of seroconversion was the ID vaccination route. The geometric mean peak antibody titer was significantly greater in the ID versus IM group: 239 IU/L (95% CI, 131 to 434) versus 78 IU/L (95% CI, 36 to 168; P < 0.001). There was a trend toward longer duration of seroprotection with ID vaccination. ID vaccine was safe and well tolerated. Inability to distinguish whether the mechanism of the greater efficacy of ID vaccination was the cumulative effect of multiple injections or route of administration; use of anti-HBs as a surrogate marker of protection; lack of evidence of long-term protection. Significantly greater seroconversion rates and peak antibody titers can be achieved with ID compared with IM vaccination in hemodialysis patients nonresponsive to primary vaccination. ID vaccination should become the standard of care in this setting.

  14. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy

    PubMed Central

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi AJO; Moriguchi-Jeckel, Cristina M; de Vries, Erik FJ

    2017-01-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants. PMID:28653857

  15. Anti-inflammatory treatment for major depressive disorder: implications for patients with an elevated immune profile and non-responders to standard antidepressant therapy.

    PubMed

    Kopschina Feltes, Paula; Doorduin, Janine; Klein, Hans C; Juárez-Orozco, Luis Eduardo; Dierckx, Rudi Ajo; Moriguchi-Jeckel, Cristina M; de Vries, Erik Fj

    2017-09-01

    Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non-responsiveness to antidepressants ranging from 30-50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants. Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic-pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre-clinical and clinical studies that have provided support for treatment with non-steroidal anti-inflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants.

  16. Intravenous augmentative citalopram versus clomipramine in partial/nonresponder depressed patients: a short-term, low dose, randomized, placebo-controlled study.

    PubMed

    Altamura, Alfredo Carlo; Dell'Osso, Bernardo; Buoli, Massimiliano; Zanoni, Silvia; Mundo, Emanuela

    2008-08-01

    The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to

  17. Management of Hepatitis C Virus/HIV Coinfection Among People Who Use Drugs in the Era of Direct-Acting Antiviral–Based Therapy

    PubMed Central

    Taylor, Lynn E.; Swan, Tracy; Matthews, Gail V.

    2013-01-01

    Where active antiretroviral therapy (ART) is accessible, human immunodeficiency virus (HIV) is a survivable illness and effective ART can reduce HIV transmission. Chronic hepatitis C virus (HCV) has emerged as a threat to the survival of individuals harboring both HCV and HIV, due to high prevalence and aggressive disease course. The HCV/HIV coinfection epidemic has been driven by people who inject drugs (PWID), although incident HCV is rising among HIV-infected men who have sex with men in the absence of drug injection. Coinfected individuals warrant aggressive treatment of both viruses; although early ART initiation is recommended to reduce the rate of liver disease progression, the most effective way to decrease HCV-related morbidity and mortality in coinfection is to achieve HCV viral eradication. Direct-acting antiviral (DAA) agents will soon revolutionize HCV treatment. Clinical data are needed regarding the efficacy of DAAs in coinfected PWID. Drug–drug interaction studies between ART, DAAs, and opiate substitution therapy must be expedited. Coinfected PWID should have equitable and universal access to HIV/AIDS, HCV, and addiction prevention, care, and treatment. Essential basic steps include improving screening for both infections and engaging coinfected PWID in HIV and HCV care early after diagnoses. Developing strategies to expand access to HCV therapy for coinfected PWID is imperative to stem the HCV epidemic and limit the morbidity and mortality of those at greatest risk for HCV disease progression. The ultimate goal must be the elimination of HCV from all coinfected PWID. PMID:23884059

  18. Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment.

    PubMed

    Muñoz de Rueda, Paloma; Fuentes Rodríguez, José Manuel; Quiles Pérez, Rosa; Gila Medina, Ana; Martín Álvarez, Ana Belén; Casado Ruíz, Jorge; Ruíz Extremera, Angeles; Salmerón, Javier

    2017-07-07

    To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). For both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). The obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL.

  19. Hepatitis C virus NS5A region mutation in chronic hepatitis C genotype 1 patients who are non-responders to two or more treatments and its relationship with response to a new treatment

    PubMed Central

    Muñoz de Rueda, Paloma; Fuentes Rodríguez, José Manuel; Quiles Pérez, Rosa; Gila Medina, Ana; Martín Álvarez, Ana Belén; Casado Ruíz, Jorge; Ruíz Extremera, Angeles; Salmerón, Javier

    2017-01-01

    AIM To determine the number of mutations in the NS5A region of the hepatitis C virus (HCV) and its relationship to the response to antiviral therapy in patients with chronic hepatitis C genotype 1 who are non-responders to two or more treatments. METHODS Sequences within HCV NS5A [PKR binding domain (PKRBD) and the interferon-sensitivity-determining region (ISDR)] were analysed via direct sequencing in a selected cohort of 72 patients, with a total of 201 treatments [interferon-alpha (IFN-α), n = 49; IFN-α + ribavirin (RBV), n = 75; pegylated (peg) IFN-α + RBV, n = 47; first-generation direct-acting antivirals (DAAs), n = 13; and second-generation DAAs, n = 17]. Of these, 48/201 achieved a sustained virological response (SVR) and 153/201 achieved no virological response (NVR). RESULTS For both regions, treatments resulting in SVR were associated with more baseline mutations than were treatments resulting in NVR (SVR vs NVR; PKRBD: 5.82 ± 3 vs 4.86 ± 2 mutations, P = 0.045; ISDR: 2.65 ± 2 vs 1.51 ± 1.7 mutations, P = 0.005). A decrease or no change in the number of mutations over time between treatments in the PKRBD or ISDR, as shown by sequencing, was associated with patients who usually failed to respond to treatment (PKRBD, P = 0.02; ISDR, P = 0.001). Moreover, patients showing a post-treatment baseline viral load > 600000 IU/mL and increased ISDR mutations with respect to the previous treatment were 9.21 times more likely to achieve SVR (P = 0.001). CONCLUSION The obtained results show that among patients who have shown no response to two or more antiviral treatments, the likelihood of achieving SVR increases with the genetic variability in the ISDR region (≥ 2 mutations or number of substitutions from the HCV-J and HCV-1 prototype), especially when the viral load is greater than 600000 IU/mL. PMID:28740342

  20. During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy.

    PubMed

    Kostadinova, Lenche; Shive, Carey L; Judge, Chelsey; Zebrowski, Elizabeth; Compan, Anita; Rife, Kelsey; Hirsch, Amy; Falck-Ytter, Yngve; Schlatzer, Daniela M; Li, Xiaolin; Chance, Mark R; Rodriguez, Benigno; Popkin, Daniel L; Anthony, Donald D

    2016-11-01

     Immune activation predicts morbidity during hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, although mechanisms underlying immune activation are unclear. Plasma levels of autotaxin and its enzymatic product, lysophosphatidic acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown.  We evaluated plasma levels of autotaxin, interleukin 6 (IL-6), soluble CD14 (sCD14), soluble CD163 (sCD163), and Mac2 binding protein (Mac2BP) during HCV infection, HIV infection, and HCV-HIV coinfection, as well as in uninfected controls, before and after HIV antiretroviral therapy (ART) initiation and during interferon-free HCV therapy.  We observed greater plasma autotaxin levels in HCV-infected and HCV-HIV-coinfected participants, compared with uninfected participants, primarily those with a higher ratio of aspartate aminotransferase level to platelet count. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA levels in HCV-infected participants and with Mac2BP levels in HCV-HIV-coinfected participants, while in HIV-infected individuals, sCD14 levels correlated with Mac2BP levels. Autotaxin, LPA, and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting interferon-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting ART for HIV infection. In vitro, LPA activated monocytes.  These data indicate that elevated levels of autotaxin and soluble markers of immune activation during HCV infection are partially reversible within 6 months of initiating interferon-free HCV treatment and that autotaxin may be causally linked to immune activation during HCV infection and HCV-HIV coinfection. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. A comparison of responders and nonresponders to oral appliance therapy for the treatment of obstructive sleep apnea.

    PubMed

    Otsuka, Ryo; Almeida, Fernanda Ribeiro de; Lowe, Alan A; Ryan, Frank

    2006-02-01

    This retrospective study compared cephalometric variables between responders and nonresponders to a titratable oral appliance (OA) in a group of subjects matched for sex, pretreatment age, and body mass index (BMI). Nine nonresponders as defined by an improvement in the apnea hypopnea index (AHI; <20%) and their individually matched responders were selected for this study. The difference in age for each matched pair was +/-5 years, and, for BMI, the difference was +/-15%. The pretreatment AHI was matched to the same category (moderate, >15 to < or =30; severe I, >30 to < or =45; and severe II, >45 AHI). Middle and inferior airway space and oropharyngeal airway cross-sectional area were significantly larger in the nonresponders. Position of the mandible relative to the cervical spine was the only significant skeletal variable and was larger in nonresponders. Changes in BMI between the groups were statistically significant; the averages were a 2.9% increase in the nonresponders and a 0.5% decrease in responders. The wider airway in nonresponders might reflect an enhanced neuromuscular compensation while awake. The weight gain in nonresponders was relatively small, but it might have reduced the effectiveness of the OA. When treating OSA patients with OA therapy, clinicians should pay particular attention to airway size and weight changes.

  2. Pegylated interferon plus ribavirin in HIV-infected patients with recurrent hepatitis C after liver transplantation: a prospective cohort study.

    PubMed

    Castells, Lluis; Rimola, Antoni; Manzardo, Christian; Valdivieso, Andrés; Montero, José Luis; Barcena, Rafael; Abradelo, Manuel; Xiol, Xavier; Aguilera, Victoria; Salcedo, Magdalena; Rodriguez, Manuel; Bernal, Carmen; Suarez, Francisco; Antela, Antonio; Olivares, Sergio; Del Campo, Santos; Laguno, Montserrat; Fernandez, José R; de la Rosa, Gloria; Agüero, Fernando; Perez, Iñaki; González-García, Juan; Esteban-Mur, Juan I; Miro, Jose M

    2015-01-01

    The aim of this study was to evaluate the results of treatment with pegylated interferon and ribavirin for the recurrence of hepatitis C after liver transplantation in HCV/HIV-coinfected patients. This was a prospective, multicentre cohort study, including 78 HCV/HIV-coinfected liver transplant patients who received treatment for recurrent hepatitis C. For comparison, we included 176 matched HCV-monoinfected patients who underwent liver transplantation during the same period of time at the same centres and were treated for recurrent hepatitis C. Antiviral therapy was discontinued prematurely in 56% and 39% (p = 0.016), mainly because of toxicity (22% and 11%, respectively; p=0.034). Sustained virological response (SVR) was achieved in 21% of the coinfected patients and in 36% of monoinfected patients (p = 0.013). For genotype 1, SVR rates were 10% and 33% (p = 0.002), respectively; no significant differences were observed for the other genotypes. A multivariate analysis based on the whole series identified HIV-coinfection as an independent predictor of lack of SVR (OR, 0.17; 95% CI, 0.06-0.42). Other predictors of SVR were donor age, pretreatment HCV viral load, HCV genotype, and early virological response. SVR was associated with a significant improvement in survival: 5-year survival after antiviral treatment was 79% for HCV/HIV-coinfected patients with SVR vs. 43% for those without (p = 0.02) and 92% vs. 60% in HCV-monoinfected patients (p < 0.001), respectively. The response to pegylated interferon and ribavirin was poorer in HCV/HIV-coinfected liver recipients, particularly those with genotype 1. However, when SVR was achieved, survival of coinfected patients increased significantly. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  3. Incidence of and factors associated with hepatocellular carcinoma among hepatitis C virus and human immunodeficiency virus coinfected patients with decompensated cirrhosis.

    PubMed

    García-García, José A; Romero-Gómez, Manuel; Girón-González, José A; Rivera-Irigoin, Robin; Torre-Cisneros, Julián; Montero, José L; González-Serrano, Mercedes; Andrade, Raúl J; Aguilar-Guisado, Manuela; Grilo, Israel; Martín-Vivaldi, Javier; Salmerón, Javier; Caballero-Granado, Francisco J; Macías, Juan; Vergara-López, Salvador; Pineda, Juan A

    2006-12-01

    We compared the incidence of and factors associated with hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-monoinfected subjects and human immunodeficiency virus (HIV)/HCV-coinfected individuals, both with decompensated cirrhosis. In a retrospective study, a cohort of 180 individuals with HIV coinfection and 1037 HCV-monoinfected patients with decompensated HCV-related cirrhosis from eight centres in Spain were analyzed. HCC was found in 234 (23%) HCV-monoinfected subjects and in four (2%) HIV-coinfected subjects (p<0.001). At the time of the first hepatic decompensation, 188 (17%) and 4 (2%) (p<0.001) patients in the former and in the latter group, respectively, showed HCC. Fifty-four (11%) patients without HCC at baseline developed such a disease during follow-up. There were no incident cases among the HIV-coinfected population. The density of incidence (95% IC) of HCC in HIV/HCV-coinfected and HCV-monoinfected patients was 0 (0-1.70) and 3.31 (2.70-4.64) cases per 100 person-years (p<0.001), respectively. Lack of HIV infection [adjusted odds risk (AOR) (95% IC)=16.7 (3.9-71.1)] and high alanine aminotransferase levels [AOR (95% IC)=2.5 (1.1-5)] were the only two independent predictors of the emergence of HCC. In the group of patients in whom the date of HCV infection could be estimated, the time elapsed until HCC diagnosis was shorter among HIV-coinfected subjects. The incidence of HCC in patients with HCV-related cirrhosis after the first hepatic decompensation is lower in HIV-coinfected patients. This is probably due to the fact that HIV infection shortens the survival of HCV-coinfected patients with end-stage liver disease to such an extent that HCC not had a chance to emerge.

  4. Boceprevir or Telaprevir Based Triple Therapy against Chronic Hepatitis C in HIV Coinfection: Real-Life Safety and Efficacy

    PubMed Central

    Neukam, Karin; Munteanu, Daniela I.; Rivero-Juárez, Antonio; Lutz, Thomas; Fehr, Jan; Mandorfer, Mattias; Bhagani, Sanjay; López-Cortés, Luis F.; Haberl, Annette; Stoeckle, Marcel; Márquez, Manuel; Scholten, Stefan; de los Santos-Gil, Ignacio; Mauss, Stefan; Rivero, Antonio; Collado, Antonio; Delgado, Marcial; Rockstroh, Juergen K.; Pineda, Juan A.

    2015-01-01

    Background and Aims Clinical trials of therapy against chronic hepatitis C virus (HCV) infection including boceprevir (BOC) or telaprevir (TVR) plus pegylated interferon and ribavirin (PR) have reported considerably higher response rates than those achieved with PR alone. This study sought to evaluate the efficacy and safety of triple therapy including BOC or TVR in combination with PR in HIV/HCV-coinfected patients under real-life conditions. Methods In a multicentre study conducted in 24 sites throughout five European countries, all HIV/HCV-coinfected patients who initiated a combination of BOC or TVR plus PR and who had at least 60 weeks of follow-up, were analyzed. Sustained virologic response 12 weeks after the scheduled end of therapy date (SVR12) and the rate of discontinuations due to adverse events (AE) were evaluated. Results Of the 159 subjects included, 127 (79.9%) were male, 45 (34.4%) were treatment-naïve for PR and 60 (45.4%) showed cirrhosis. SVR12 was observed in 31/46 (67.4%) patients treated with BOC and 69/113 (61.1%) patients treated with TVR. Overall discontinuations due to AE rates were 8.7% for BOC and 8% for TVR. Grade 3 or 4 hematological abnormalities were frequently observed; anemia 7%, thrombocytopenia 17.2% and neutropenia 16.4%. Conclusion The efficacy and safety of triple therapy including BOC or TVR plus PR under real-life conditions of use in the HIV/HCV-coinfected population was similar to what is observed in clinical trials. Hematological side effects are frequent but manageable. PMID:25923540

  5. Community-acquired pneumonia: identification and evaluation of nonresponders

    PubMed Central

    Conceição, Catarina; Póvoa, Pedro

    2013-01-01

    Community acquired pneumonia (CAP) is a relevant public health problem, constituting an important cause of morbidity and mortality. It accounts for a significant number of adult hospital admissions and a large number of those patients ultimately die, especially the population who needed mechanical ventilation or vasopressor support. Thus, early identification of CAP patients and its rapid and appropriate treatment are important features with impact on hospital resource consumption and overall mortality. Although CAP diagnosis may sometimes be straightforward, the diagnostic criteria commonly used are highly sensitive but largely unspecific. Biomarkers and microbiological documentation may be useful but have important limitations. Evaluation of clinical response is also critical especially to identify patients who fail to respond to initial treatment since these patients have a high risk of in-hospital death. However, the criteria of definition of non-response in CAP are largely empirical and frequently markedly diverse between different studies. In this review, we aim to identify criteria defining nonresponse in CAP and the pitfalls associated with this diagnosis. We also aim to overview the main causes of treatment failure especially in severe CAP and the possible strategies to identify and reassess non-responders trying to change the dismal prognosis associated with this condition. PMID:25165541

  6. Epidemiology and impact of HIV coinfection with hepatitis B and hepatitis C viruses in Sub-Saharan Africa.

    PubMed

    Matthews, Philippa C; Geretti, Anna Maria; Goulder, Philip J R; Klenerman, Paul

    2014-09-01

    Human immunodeficiency virus (HIV), Hepatitis B (HBV) and Hepatitis C (HCV) are blood-borne viruses with potentially shared routes of transmission. In high-income settings, the impact of antiretroviral therapy (ART) on survival has unmasked chronic liver disease from viral hepatitis B or hepatitis C as a leading cause of morbidity and mortality in individuals with HIV infection. It is now feared that progressive liver disease may threaten the success of ART programmes in developing countries, where HCV or HBV testing and monitoring are not yet systematic among HIV-infected patients and ART use is generally blind to these co-infections. We set out to review recent data from Sub-Saharan Africa, in order to build a detailed and up-to-date picture of the epidemiology and emerging impact of HBV and HCV coinfection in countries at the heart of the HIV pandemic. There is a preponderance of HIV/HBV coinfection compared to HIV/HCV in this region, and significant caveats exist regarding the accuracy of published HCV seroprevalence surveys. Morbidity and mortality of coinfection is significant, and may be further enhanced in African populations due to the influence of host, viral and environmental factors. Careful scrutiny of the coinfection problem is vital to inform an approach to directing resources, planning public health initiatives, providing clinical care, and guiding future research. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Long-Term Echocardiographic Response to Cardiac Resynchronization Therapy in Initial Nonresponders.

    PubMed

    Burns, Kevin V; Gage, Ryan M; Curtin, Antonia E; Bank, Alan J

    2015-12-01

    The aim of this study was to investigate the frequency and clinical implications of a delayed echocardiographic response to cardiac resynchronization therapy (CRT). Long-term prognosis for CRT patients is routinely based on the assessment of echocardiograms after 6 to 12 months of therapy. Some patients, however, may require a longer period of therapy before echocardiographic improvements are detectable. This observational study included all patients with heart failure (HF) receiving a CRT device at a single center from 2003 to 2011. Eligible patients met current indications and had technically adequate echocardiograms from before implantation, approximately 1 year after implantation (mid-term), and ≥3 years after implantation (long-term). A positive echocardiographic response to CRT was defined as a reduction in left ventricular end-systolic volume ≥15%. All-cause mortality was compared for patients in 3 response groups: mid-term responders, long-term responders, and nonresponders. During this study, 294 patients met the study criteria. Of the 120 patients who were nonresponders after 1 year, 52 (43%) experienced a delayed positive response. Delayed, long-term responders had mortality and hospitalization rates similar to mid-term responders and significantly lower than nonresponders. Among patients surviving at least 3 years after implantation of a CRT device and with echocardiographic follow-up, a significant portion of nonresponders after 1 year of CRT experience a delayed echocardiographic response after a longer period of time. Survival and hospitalization rates were similar for all echocardiographic responders, regardless of the time at which the response occurred. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Incidence, definition, diagnosis, and management of the cardiac resynchronization therapy nonresponder.

    PubMed

    Zhang, Qing; Zhou, Yujie; Yu, Cheuk-Man

    2015-01-01

    Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with mild-to-severe heart failure. However, up to 40% of CRT recipients are nonresponders. This review addresses important aspects with regard to the identification and management of CRT nonresponders. Mid-term clinical or echocardiographic nonresponse is associated with worse clinical outcomes during the extended follow-up. A number of predictors are indicative of CRT response, which include patient characteristics, electrical determinants, and imaging techniques from preimplant to postimplant period, and can be grouped as modifiable and nonmodifiable contributors to treatment response. Advanced age, male sex, ischemic cause, end-stage heart failure, inadequate electrical delay, and absence of mechanical dyssynchrony are regarded as unfavorable but nonmodifiable factors, for which considering underutilization of CRT by refining patient selection is reasonable. On the contrary, more efforts should be made to optimize patient management by correcting those modifiable factors, such as suboptimal medical therapy, uncontrolled atrial fibrillation, left ventricular lead dislodgement or inappropriate location, loss of biventricular capture, and lack of device optimization. Proper management and careful selection of CRT recipients will transform a proportion of treatment nonresponders into responders, which is vital to improve patients' outcome.

  9. Impact of CT-apelin and NT-proBNP on identifying non-responders to cardiac resynchronization therapy.

    PubMed

    Kosztin, Annamária; Széplaki, Gábor; Kovács, Attila; Földes, Gábor; Szokodi, István; Vivien Nagy, Klaudia; Kutyifa, Valentina; Fórizs, Éva; Végh, Eszter M; Gellér, László; Becker, Dávid; Aradi, Dániel; Merkely, Béla

    Assessment of response to cardiac resynchronization therapy (CRT) is essential. To assess the predictive value of CT-apelin together with NT-proBNP in patients undergoing CRT. Serum CT-apelin and NT-proBNP were measured by ELISA before, and six months after CRT. Primary endpoint was non-response (<4% increase in LVEF) after six months. From 81 patients, 15 proved to be non-responders. Six-month CT-apelin was superior compared to NT-proBNP in identifying non-responders by multivariate ROC (CT-apelin: p = 0.01, NT-proBNP: p = 0.13) and by logistic regression (CT-apelin: p = 0.01, NT-proBNP: p = 0.41) analyses. Six-month CT-apelin might be a valuable novel biomarker in identifying non-responders to CRT that was superior to NT-proBNP.

  10. Pacemaker optimization in nonresponders to cardiac resynchronization therapy: left ventricular pacing as an available option.

    PubMed

    Gage, Ryan M; Burns, Kevin V; Vatterott, Daniel B; Kubo, Spencer H; Bank, Alan J

    2012-06-01

    Echocardiographic (ECHO)-guided pacemaker optimization (PMO) in cardiac resynchronization therapy (CRT) nonresponders acutely improves left ventricular (LV) function. However, the chronic results of LV pacing in this group are less understood. We retrospectively studied 28 CRT nonresponders optimized based on ECHO to LV pacing and compared them to 28 age- and gender-matched patients optimized to biventricular (BiV) pacing. ECHOs with tissue Doppler imaging assessed LV hemodynamics before, immediately after, and 29 ± 16 months after PMO. Also, 56 age- and gender-matched CRT responders were included for comparison of clinical outcomes. PMO resulted in acute improvements in longitudinal LV systolic function and several measures of dyssynchrony, with greater improvements in the LV paced group. Chronic improvements in ejection fraction (EF) (3.2 ± 7.7%), and left ventricle end-systolic volume (LVESV) (-11 ± 36 mL) and one dyssynchrony measure were seen in the combined group. Chronically, both LV and BiV paced patients improved some measures of systolic function and dyssynchrony although response varied between the groups. Survival at 3.5 years was similar (P = 0.973) between the PMO (58%) and nonoptimized groups (58%) but survival free of cardiovascular hospitalization was significantly (P = 0.037) better in the nonoptimized group. CRT nonresponders undergoing PMO to either LV or BiV pacing have acute improvements in longitudinal systolic function and some measures of dyssynchrony. Some benefits are sustained chronically, with improvements in EF, LVESV, and dyssynchrony. A strategy of ECHO-guided PMO results in survival for CRT nonresponders similar to that of CRT patients not referred for PMO. ©2012, The Authors. Journal compilation ©2012 Wiley Periodicals, Inc.

  11. Brain Changes in Responders vs. Non-Responders in Chronic Migraine: Markers of Disease Reversal

    PubMed Central

    Hubbard, Catherine S.; Becerra, Lino; Smith, Jonathan H.; DeLange, Justin M.; Smith, Ryan M.; Black, David F.; Welker, Kirk M.; Burstein, Rami; Cutrer, Fred M.; Borsook, David

    2016-01-01

    The aim of this study was to identify structural and functional brain changes that accompanied the transition from chronic (CM; ≥15 headache days/month) to episodic (EM; <15 headache days/month) migraine following prophylactic treatment with onabotulinumtoxinA (BoNT-A). Specifically, we examined whether CM patients responsive to prophylaxis (responders; n = 11), as evidenced by a reversal in disease status (defined by at least a 50% reduction in migraine frequency and <15 headache days/month), compared to CM patients whose migraine frequency remained unchanged (non-responders; n = 12), showed differences in cortical thickness using surface-based morphometry. We also investigated whether areas showing group differences in cortical thickness displayed altered resting-state functional connectivity (RS-FC) using seed-to-voxel analyses. Migraine characteristics measured across groups included disease duration, pain intensity and headache frequency. Patient reports of headache frequency over the 4 weeks prior to (pre-treatment) and following (post-treatment) prophylaxis were compared (post minus pre) and this measure served as the clinical endpoint that determined group assignment. All patients were scanned within 2 weeks of the post-treatment visit. Results revealed that responders showed significant cortical thickening in the right primary somatosensory cortex (SI) and anterior insula (aINS), and left superior temporal gyrus (STG) and pars opercularis (ParsOp) compared to non-responders. In addition, disease duration was negatively correlated with cortical thickness in fronto-parietal and temporo-occipital regions in responders but not non-responders, with the exception of the primary motor cortex (MI) that showed the opposite pattern; disease duration was positively associated with MI cortical thickness in responders versus non-responders. Our seed-based RS-FC analyses revealed anti-correlations between the SI seed and lateral occipital (LOC) and dorsomedial

  12. Clinical outcomes following switch from venlafaxine ER to desvenlafaxine in nonresponders and responders.

    PubMed

    Guico-Pabia, C J; Jiang, Q; Ninan, P T; Thase, M E

    2011-09-01

    This post hoc analysis examined efficacy and tolerability of open-label desvenlafaxine in patients with major depressive disorder switched from blinded placebo, venlafaxine extended release (ER), or desvenlafaxine. Patients who completed 8 weeks of double-blind therapy with placebo (n = 176), venlafaxine ER (n = 175), or desvenlafaxine (n = 143) enrolled in a 10-month, open-label extension study and received desvenlafaxine 200 to 400 mg/d. Efficacy (17-item Hamilton Depression Rating Scale [HDRS(17)]) was assessed separately for nonresponders and responders to double-blind treatment. Tolerability during the first month of open-label desvenlafaxine was assessed. Among nonresponders (n = 134) to double-blind placebo, venlafaxine ER, and desvenlafaxine, mean decreases in HDRS(17) scores were -10.9, -7.3, and -7.7, respectively; HDRS(17) response rates were 67%, 53%, and 48%, respectively. Although responders (n = 360) to double-blind placebo, venlafaxine ER, and desvenlafaxine had more modest decreases on the HDRS(17), response rates were higher (84%, 87%, and 83%, respectively). Rates of adverse events were highest during week 1, and decreased afterward for the remainder of the first month of treatment. Among nonresponders to 8 weeks of double-blind venlafaxine ER, desvenlafaxine, or placebo, 48% to 67% subsequently responded to open-label desvenlafaxine. Over 80% of responders to double-blind therapy maintained response on open-label desvenlafaxine. The switch from venlafaxine ER to desvenlafaxine was well tolerated.

  13. Similar effectiveness of direct-acting antiviral against hepatitis C virus in patients with and without HIV infection.

    PubMed

    Montes, María Luisa; Olveira, Antonio; Ahumada, Adriana; Aldámiz, Teresa; García-Samaniego, Javier; Clemente, Ana; Berenguer, Juan; González-García, Juan; Martín-Carbonero, Luz

    2017-06-01

    We compared the baseline characteristics, effectiveness, and tolerance of direct-acting antiviral drug (DAA)-based regimens taken by hepatitis C virus (HCV)-monoinfected and HCV/HIV-coinfected individuals in clinical practice. We performed a prospective observational study in two tertiary centres in Madrid, Spain, which included all HCV-monoinfected and HCV/HIV-coinfected patients undergoing HCV treatment with all-oral DAA regimens in a routine clinical setting, from April 2015 to November 2015. We evaluated sustained virological response 12 weeks after the end of therapy (SVR12), adverse events, and baseline and treatment characteristics. The study population comprised 1634 patients: 1152 HCV-monoinfected patients (70%) and 482 HCV/HIV-coinfected patients (30%). Fifty percent had cirrhosis, and 47% were peginterferon/ribavirin-experienced. HCV/HIV-coinfected patients were younger [median age (interquartile range) 51 (48-54) years vs. 59 (50-68) years; P < 0.001), more frequently male (76 vs. 54%; P < 0.001), and infected with genotypes 1a (37 vs. 17%; P < 0.001), 3 (15 vs. 7%; P < 0.001), and 4 (23 vs. 4%; P < 0.001). One of every three patients took ribavirin. SVR12 was 94% (95% confidence interval 91.7-96%) and 97% (95% confidence interval 95.7-99.4%) in coinfected and monoinfected patients, respectively, with no significant differences between the groups after adjustment for cirrhosis, genotype, and DAA combination. DAA-based regimens were well tolerated, and only 1% of patients had severe adverse events, with no differences between the populations. HCV/HIV-infected patients treated with all-oral DAA combinations achieved high rates of SVR12 that were similar to those of HCV-monoinfected patients under real-life conditions. Safety and tolerance were excellent, even in patients with end-stage liver disease.

  14. Complexity and Catalytic Efficiency of Hepatitis C Virus (HCV) NS3 and NS4A Protease Quasispecies Influence Responsiveness to Treatment with Pegylated Interferon plus Ribavirin in HCV/HIV-Coinfected Patients▿†

    PubMed Central

    Aparicio, Ester; Franco, Sandra; Parera, Mariona; Andrés, Cristina; Tural, Cristina; Clotet, Bonaventura; Martínez, Miguel Angel

    2011-01-01

    The role of the hepatitis C virus (HCV) NS3/4A protease in ablating the signaling pathway involved in the production of alpha/beta interferon (IFN-α/β) suggests a relationship between NS3/4A proteolytic activity and a patient's response to IFN-based therapy. To identify viral factors associated with the HCV treatment response, we analyzed the pretreatment NS3/4A protease gene quasispecies composition of 56 HCV genotype 1–HIV-1-coinfected patients treated in our clinic with pegylated IFN (pegIFN) plus ribavirin (RBV). The catalytic efficiency of the dominant (i.e., the most abundant) quasispecies was also assayed for Cardif cleavage and correlated with treatment outcome. A total of 1,745 clones were isolated and sequenced. Significantly less nucleotide quasispecies heterogeneity and lower Shannon entropy values were detected within the responder group (P < 0.05). A correlation was also found between the efficiency of NS3/4A protease Cardif cleavage and therapy outcome. Proteases from sustained responder patients were more efficient at processing Cardif (mean ± standard error of the mean [SEM], 0.8960 ± 0.05568; n = 19) than proteases from nonresponders (mean ± SEM, 0.7269 ± 0.05306; n = 37; P < 0.05). Finally, the amino acid p distance (the proportion [p] of nucleotide sites at which two sequences being compared are different) was significantly shorter in patients with an interleukin-28B (IL-28B) risk allele (P < 0.01), suggesting that IL-28B risk allele carriers exert a lower positive selection pressure on the NS3/4A protease. NS3/4A protease efficiency in cleaving Cardif may be associated with the pegIFN-RBV treatment response, as shown in our cohort of HIV-HCV-coinfected patients. Greater NS3/4A nucleotide heterogeneity and higher Shannon entropy values in nonresponders suggest that less HCV quasispecies complexity may favor a better response to pegIFN-RBV. PMID:21471227

  15. Locally advanced rectal cancer: predicting non-responders to neoadjuvant chemoradiotherapy using apparent diffusion coefficient textures.

    PubMed

    Liu, Ming; Lv, Han; Liu, Li-Heng; Yang, Zheng-Han; Jin, Er-Hu; Wang, Zhen-Chang

    2017-07-01

    The purpose of the study is to evaluate whether apparent diffusion coefficient (ADC) textures could identify patient with locally advanced rectal cancer (LARC) who would not respond to neoadjuvant chemoradiotherapy (NCRT). Twenty-six patients who underwent MRI including diffusion-weighted imaging at a 3.0 T system before NCRT were enrolled. Texture analysis of pre-therapy ADC mapping was carried out, and a total of 133 ADC textures as well as routine mean ADC value of the primary tumor were extracted for each patient. Texture parameters and mean ADC were compared between responsive group and non-responsive group. Logistic regression was used to determine the independent predictors for non-responders. Receiver operating characteristic curve (ROC) was performed to evaluate the predictive performance of the significant parameters. Eighteen of the 133 texture parameters significantly differed between responsive and non-responsive groups (p < 0.05). Further, energy variance and SdGa47 were identified as independent predictors for non-responders to NCRT; this logistic model achieved an area under the curve (AUC) of 0.908. Texture analysis based on pre-therapy ADC mapping could potentially be helpful to identify patients with LARC who would not respond to NCRT.

  16. Prevalence of and factors associated with hepatic steatosis in patients coinfected with hepatitis C virus and HIV: Agence Nationale pour la Recherche contre le SIDA et les hépatites virales CO3 Aquitaine Cohort.

    PubMed

    Neau, Didier; Winnock, Maria; Castéra, Laurent; Bail, Brigitte Le; Loko, Marc-Arthur; Géraut, Laurent; Dupon, Michel; Ragnaud, Jean-Marie; Lacoste, Denis; Lafon, Marie-Edith; Bioulac-Sage, Paulette; Dabis, François

    2007-06-01

    Hepatic steatosis is a common feature in liver biopsies from patients with chronic hepatitis C and is associated with fibrosis progression. Patients with HIV infection and hepatitis C virus (HCV) coinfection have more rapid progression of liver fibrosis than patients with HCV infection alone. The prevalence and factors associated with hepatic steatosis are not well defined in HCV-HIV-coinfected patients. Steatosis was assessed among 148 HCV-HIV-coinfected patients of the Aquitaine Cohort. Steatosis was graded as follows: none, mild (1%-10% of hepatocytes), moderate (11%-30%), severe (31%-60%), and massive (more than 60%). Epidemiologic, clinical, biologic, and therapeutic data were retrieved from the cohort database to investigate the risk factors. Steatosis was present in 67% of patients (95% confidence interval [CI]: 59% to 74%) and was at least moderate in 30% (95% CI: 23% to 38%). Steatosis was macrovesicular or mixed (macro- and microvesicular) in 40.5% and 52.8% of patients, respectively. Necroinflammatory activity was the only factor independent of steatosis (adjusted odds ratio = 5.3, 95% CI: 1.6 to 17.9). When necroinflammatory activity was removed from the model, HCV genotype 3 and body mass index (BMI) were significantly associated with steatosis. Liver inflammation, HCV genotype 3, and BMI are associated with steatosis, a common finding in HCV-HIV-coinfected patients.

  17. Epidemiological Characteristics and Clinical Outcome of HIV-Related Tuberculosis in a Population of TB Patients in South-western Nigeria.

    PubMed

    Olowe, Olugbenga A; Makanjuola, Olufunmilola B; Adekanmi, Adeniyi S; Adefioye, Olusola J; Olowe, Rita A

    2017-06-01

    Tuberculosis (TB) is the second leading cause of death from infectious disease globally with its impact more dramatic in resource limited settings. Individuals with human immunodeficiency virus (HIV) infection who also develop tuberculosis represent a significant challenge to TB control. This study was carried out to determine the prevalence of TB-HIV coinfection and pattern of infection among TB patients. We also compared treatment outcome among coinfected patients with those not coinfected. A six-year retrospective review of records of patients managed at the Tuberculosis Treatment Center of the LAUTECH Teaching Hospital, South-Western Nigeria from January 2009 to December 2014 was carried out. One hundred and five (26.3%) of the 399 TB patients seen in the study period were coinfected with HIV. About 10% of the subjects had extrapulmonary tuberculosis. Treatment failure was significantly worse among patients who had both HIV and TB compared with those who had TB only (49.5% vs. 32%, p = 0.001). Death rate was also higher in the coinfected individuals implying a poorer clinical outcome. High prevalence of TB-HIV coinfection and poor treatment outcome in this group of individuals, though predictable, calls for a more concerted effort in the management of TB-HIV coinfection.

  18. Immunoglobulin treatment in post-polio syndrome: Identification of responders and non-responders.

    PubMed

    Östlund, Gunilla; Broman, Lisbet; Werhagen, Lars; Borg, Kristian

    2015-09-01

    To define and characterize responders and non-responders in a group of 124 patients with post-polio syndrome who received a single treatment with intravenous immunoglobulin. Open trial, prospective follow-up study. Clinical examination and data from medical records. Short Form 36 (SF-36), Physical Activity Scale for the Elderly (PASE) and visual analogue scale (VAS) measured quality of life, physical activity and intensity of pain, respectively. Data were obtained before treatment and at 6-month follow-up. Two responder groups were identified with the outcome SF-36 Vitality and 3 with Bodily pain, respectively. Forty-five percent were positive-responders, identified before treatment by reduced physical function, muscle atrophy in the lower extremities, higher levels of fatigue and pain, and a VAS pain score above 20. Negative-responders were identified by good physical function and mental health, lesser muscle atrophy in the lower extremities, and low levels of fatigue and pain. Intravenous immunoglobulin is a biological intervention, and therefore it is important to be able to identify responders and non-responders. In order to maximize a positive outcome it is suggested that patients with a high level of fatigue and/or pain and reduced physical function are selected.

  19. Early identification of non-responding locally advanced breast tumors receiving neoadjuvant chemotherapy

    NASA Astrophysics Data System (ADS)

    Van de Giessen, Martijn; Schaafsma, Boudewijn E.; Charehbili, Ayoub; Smit, Vincent T. H. B. M.; Kroep, Judith R.; Lelieveldt, Boudewijn P. F.; Liefers, Gerrit-Jan; Chan, Alan; Löwik, Clemens W. G. M.; Dijkstra, Jouke; van de Velde, Cornelis J. H.; Wasser, Martin N. J. M.; Vahrmeijer, Alexander L.

    2015-02-01

    Diffuse optical spectroscopy (DOS) may be advantageous for monitoring tumor response during chemotherapy treatment, particularly in the early treatment stages. In this paper we perform a second analysis on the data of a clinical trial with 25 breast cancer patients that received neoadjuvant chemotherapy. Patients were monitored using delayed contrast enhanced MRI and additionally with diffuse optical spectroscopy at baseline, after 1 cycle of chemotherapy, halfway therapy and before surgery. In this analysis hemoglobin content between tumor tissue and healthy tissue of the same breast is compared on all four monitoring time points. Furthermore, the predictive power of the tumor-healthy tissue difference of HbO2 for non-responder prediction is assessed. The difference in HbO2 content between tumor and healthy tissue was statistically significantly higher in responding tumors than in non-responding tumors at baseline (10.88 vs -0.57 μM, P=0.014) and after one cycle of chemotherapy (6.45 vs -1.31 μM, P=0.048). Before surgery this difference had diminished. In the data of this study, classification on the HbO2 difference between tumor and healthy tissue was able to predict tumor (non-)response at baseline and after 1 cycle with an area-under-curve of 0.95 and 0.88, respectively. While this result suggests that tumor response can be predicted before chemotherapy onset, one should be very careful with interpreting these results. A larger patient population is needed to confirm this finding.

  20. The Effect of Nonrespondents on a Self-Administered Mail Survey.

    ERIC Educational Resources Information Center

    Krushat, W. Mark; Molnar, John I.

    1993-01-01

    After a mailed questionnaire and two follow-ups, hard-core survey nonrespondents were contacted to ask why they had not responded and what they would have answered had they responded. Results from 28 subjects indicate that efforts to pursue nonrespondents may be unnecessary, because bias resulting from nonresponse appeared minimal. (SLD)

  1. A comparison of small monetary incentives to convert survey non-respondents: a randomized control trial

    PubMed Central

    2011-01-01

    Background Maximizing response rates is critically important in order to provide the most generalizable and unbiased research results. High response rates reduce the chance of respondents being systematically different from non-respondents, and thus, reduce the risk of results not truly reflecting the study population. Monetary incentives are often used to improve response rates, but little is known about whether larger incentives improve response rates in those who previously have been unenthusiastic about participating in research. In this study we compared the response rates and cost-effectiveness of a $5 versus $2 monetary incentive accompanying a short survey mailed to patients who did not respond or refused to participate in research study with a face-to-face survey. Methods 1,328 non-responders were randomly assigned to receive $5 or $2 and a short, 10-question survey by mail. Reminder postcards were sent to everyone; those not returning the survey were sent a second survey without incentive. Overall response rates, response rates by incentive condition, and odds of responding to the larger incentive were calculated. Total costs (materials, postage, and labor) and incremental cost-effectiveness ratios were also calculated and compared by incentive condition. Results After the first mailing, the response rate within the $5 group was significantly higher (57.8% vs. 47.7%, p < .001); after the second mailing, the difference narrowed by 80%, resulting in a non-significant difference in cumulative rates between the $5 and $2 groups (67.3% vs. 65.4%, respectively, p = .47). Regardless of incentive or number of contacts, respondents were significantly more likely to be male, white, married, and 50-75 years old. Total costs were higher with the larger versus smaller incentive ($13.77 versus $9.95 per completed survey). Conclusions A $5 incentive provides a significantly higher response rate than a $2 incentive if only one survey mailing is used but not if two survey

  2. Cost-effectiveness of early responders versus early nonresponders to atypical antipsychotic therapy

    PubMed Central

    Peng, Xiaomei; Ascher-Svanum, Haya; Faries, Douglas E; Stauffer, Virginia L; Kollack-Walker, Sara; Kinon, Bruce J; Kane, John M

    2011-01-01

    Background: To compare the cost-effectiveness of treating early responders versus early nonresponders to an atypical antipsychotic (risperidone) and the cost-effectiveness of treating early nonresponders maintained on risperidone versus those switched to olanzapine. Methods: This post hoc analysis used data from a randomized, double-blind, 12-week schizophrenia study (Study Code: HGMN, n = 628). Participants were initially assigned to risperidone therapy. Early response was defined as a ≥ 20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score from baseline to two weeks. Early responders continued on risperidone, whereas early nonresponders were randomized in a double-blind manner to continue on risperidone or switch to olanzapine for 10 additional weeks. Early responders and early nonresponders maintained on risperidone were compared for health-state utilities (benefits) and total cost over the 12-week study; early nonresponders maintained on risperidone or switched to olanzapine were compared from randomization (10-week period). Utilities were derived from the PANSS and adverse events. Mixed models were used to assess group differences in utilities. Treatment costs were calculated based on health states. Incremental cost-effectiveness ratios were then utilized to compare treatment groups. Results: Early responders to risperidone had significantly greater total utility and lower total treatment costs than early nonresponders to risperidone. Compared with early nonresponders who continued on risperidone, those who were switched to olanzapine had significantly higher total utility scores at endpoint and numerically lower total treatment costs, reflecting significantly lower nonmedication treatment costs, even though medication costs were significantly higher compared with generic risperidone. Conclusion: Treatment of early responders was more cost-effective than treatment of early nonresponders to atypical antipsychotic therapy. Switching

  3. On the nature of non-responding in discrimination learning with and without errors1

    PubMed Central

    Terrace, H. S.

    1974-01-01

    In human subjects, discrimination learning with errors results in active responding incompatible with the reinforced response. The direction of such incompatible behavior is opposite to that of the reinforced response. Responding occurs only during the stimulus correlated with extinction. The frequency of active non-responding is maximal shortly after the start of discrimination training (the time at which the frequency of errors decreases most rapidly) and approaches zero as discrimination training continues. The magnitude of behavioral contrast is not related systematically to the number of errors. Instead it is related directly to the frequency of active non-responding. Active non-responding appears to be motivated by the aversiveness of self-produced frustration, in the sense that active non-responding allows the subject to avoid the aversiveness of non-reinforced responding. ImagesFig. 1.Fig. 2. PMID:16811774

  4. Pretreatment cognitive and neural differences between sapropterin dihydrochloride responders and non-responders with phenylketonuria.

    PubMed

    Hawks, Zoë; Shimony, Joshua; Rutlin, Jerrel; Grange, Dorothy K; Christ, Shawn E; White, Desirée A

    2017-09-01

    Sapropterin dihydrochloride (BH4) reduces phenylalanine (Phe) levels and improves white matter integrity in a subset of individuals with phenylketonuria (PKU) known as "responders." Although prior research has identified biochemical and genotypic differences between BH4 responders and non-responders, cognitive and neural differences remain largely unexplored. To this end, we compared intelligence and white matter integrity prior to treatment with BH4 in 13 subsequent BH4 responders with PKU, 16 subsequent BH4 non-responders with PKU, and 12 healthy controls. Results indicated poorer intelligence and white matter integrity in non-responders compared to responders prior to treatment. In addition, poorer white matter integrity was associated with greater variability in Phe across the lifetime in non-responders but not in responders. These results underscore the importance of considering PKU as a multi-faceted, multi-dimensional disorder and point to the need for additional research to delineate characteristics that predict response to treatment with BH4.

  5. Consensus Interferon for Recurrent Hepatitis C Infection in Nonresponders to Peginterferon and Ribavirin After Liver Transplant.

    PubMed

    Nordstrom, Eric M; Biggins, Scott W; Gralla, Jane; Rosen, Hugo R; Everson, Gregory T; Burton, James R

    2015-12-01

    Hepatitis C virus infection universally recurs in liver transplant recipients. Peginterferon/ribavirin achieves a sustained virologic response rate of 30% in recipients infected with hepatitis C virus genotype 1. Consensus-interferon plus ribavirin yields sustained virologic response rates to 30% in patients failing to achieve sustained virologic response with peginterferon/ribavirin pretransplant, but it has not been studied posttransplant. We sought to evaluate the efficacy and tolerability of consensus-interferon and ribavirin in treating posttransplant hepatitis C virus. Clinical, laboratory, and virologic data were collected retrospectively from all patients who received at least 1 dose of consensus-interferon after transplant between January 2008 and December 2011. A standardized treatment protocol was used. The primary aim was sustained virologic response defined by undetectable hepatitis C virus RNA at 24 weeks after completing therapy. Twenty-three patients were treated with consensus-interferon/ribavirin; 15 with prior nonresponse (87%) or breakthrough (6.7%) during peginterferon/ribavirin, and 8 as initial therapy. The intention-to-treat sustained virologic response with consensus-interferon was 30%. Anemia, leukopenia, and growth factor requirement were similar between peginterferon and consensus-interferon cohorts. Consensus-interferon may rescue liver recipients who are nonresponders to peginterferon-based therapy. The efficacy of interferon-based treatment regimens may benefit from substitution of consensus-interferon for peginterferon.

  6. HIV treatment cascade in tuberculosis patients

    PubMed Central

    Lessells, Richard J.; Swaminathan, Soumya; Godfrey-Faussett, Peter

    2015-01-01

    Purpose of review Globally, the number of deaths associated with tuberculosis (TB) and HIV coinfection remains unacceptably high. We review the evidence around the impact of strengthening the HIV treatment cascade in TB patients and explore recent findings about how best to deliver integrated TB/HIV services. Recent findings There is clear evidence that the timely provision of antiretroviral therapy (ART) reduces mortality in TB/HIV coinfected adults. Despite this, globally in 2013, only around a third of known HIV-positive TB cases were treated with ART. Although there is some recent evidence exploring the barriers to achieve high coverage of HIV testing and ART initiation in TB patients, our understanding of which factors are most important and how best to address these within different health systems remains incomplete. There are some examples of good practice in the delivery of integrated TB/HIV services to improve the HIV treatment cascade. However, evidence of the impact of such strategies is of relatively low quality for informing integrated TB/HIV programming more broadly. In most settings, there remain barriers to higher-level organizational and functional integration. Summary There remains a need for commitment to patient-centred integrated TB/HIV care in countries affected by the dual epidemic. There is a need for better quality evidence around how best to deliver integrated services to strengthen the HIV treatment cascade in TB patients, both at primary healthcare level and within community settings. PMID:26352390

  7. Pathological Role of Anti-CD4 Antibodies in HIV-Infected Immunologic Nonresponders Receiving Virus-Suppressive Antiretroviral Therapy.

    PubMed

    Luo, Zhenwu; Li, Zhen; Martin, Lisa; Wan, Zhuang; Meissner, Eric G; Espinosa, Enrique; Wu, Hao; Yu, Xiaocong; Fu, Pingfu; Julia Westerink, Maria Anna; Kilby, J Michael; Wu, Jennifer; Huang, Lei; Heath, Sonya L; Li, Zihai; Jiang, Wei

    2017-07-01

    Increased mortality and morbidity occur among human immunodeficiency virus (HIV)-infected patients in whom CD4+ T-cell counts do not increase despite viral suppression with antiretroviral therapy (ART). Here we identified an underlying mechanism. Significantly elevated plasma levels of anti-CD4 immunoglobulin G (IgG) were found in HIV-positive immunologic nonresponders (ie, HIV-positive individuals with CD4+ T-cell counts of ≤350 cells/μL), compared with levels in HIV-positive immunologic responders (ie, HIV-positive individuals with CD4+ T-cell counts of ≥500 cells/μL) and healthy controls. Higher plasma level of anti-CD4 IgG correlated with blunted CD4+ T-cell recovery. Furthermore, purified anti-CD4 IgG from HIV-positive immunologic nonresponders induced natural killer (NK) cell-dependent CD4+ T-cell cytolysis and apoptosis through antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro. We also found that anti-CD4 IgG-mediated ADCC exerts greater apoptosis of naive CD4+ T cells relative to memory CD4+ T cells. Consistently, increased frequencies of CD107a+ NK cells and profound decreases of naive CD4+ T cells were observed in immunologic nonresponders as compared to responders and healthy controls ex vivo. These data indicate that autoreactive anti-CD4 IgG may play an important role in blunted CD4+ T-cell reconstitution despite effective ART. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  8. Hepatitis C virus NS3/4A quasispecies diversity in acute hepatitis C infection in HIV-1 co-infected patients.

    PubMed

    Nevot, M; Boesecke, C; Parera, M; Andrés, C; Franco, S; Revollo, B; Ingiliz, P; Tural, C; Clotet, B; Rockstroh, J K; Martinez, M A

    2014-06-01

    The growing number of cases of acute hepatitis C (AHC) infections among human immunodeficiency virus type 1 (HIV-1)-positive men who have sex with men (MSM) in the last 10 years has promoted the search for predictors of AHC clearance as well as for epidemiological networks of viral transmission. We characterized the diversity and catalytic efficiency of HCV NS3/4A protease quasispecies in AHC patients coinfected with HIV-1. Plasma samples obtained at HCV diagnosis from 18 MSM HIV-coinfected patients with AHC were studied. Five HCV monoinfected patient samples with AHC were also investigated. An average of 39 clones from each sample was analysed. The catalytic efficiency of the dominant quasispecies (i.e. the most abundant) from each quasispecies was also assayed for mitochondrial antiviral signalling protein (MAVS) cleavage. Phylogenetic analysis identified two clusters of patients with highly related viruses, suggesting a common source of HCV infection. None of the 18 MSM HIV-coinfected patients spontaneously cleared HCV, although 78% of the treated patients achieved a sustained virological response after early treatment with pegylated interferon (pegIFN) plus ribavirin (RBV). The synonymous-nonsynonymous (ds/dn) mutation ratio, a marker of selective pressure, was higher in AHC compared to 26 HIV-1-infected men with genotype 1a chronic hepatitis C (CHC) (P < 0.0001). NS3/4A proteases from AHC patients also exhibited higher catalytic efficiency compared to CHC patients (P < 0.0001). No differences were found when ds/dn mutation ratios and NS3/4A protease catalytic efficiencies from AHC HIV-coinfected patients were compared with AHC monoinfected patients. The presence of epidemiological networks of HCV transmission was confirmed among HIV-1-positive MSM. In addition, substantial genetic diversity was demonstrated in AHC. NS3/4A protease efficiency cleaving MAVS may be associated with virus transmission and response to pegIFN/RBV treatment.

  9. The Influence of Clinical and Biological Factors on Transfusion-Associated Non-ABO Antigen Alloimmunization: Responders, Hyper-Responders, and Non-Responders.

    PubMed

    Gehrie, Eric A; Tormey, Christopher A

    2014-11-01

    In the context of transfusion medicine, alloimmunization most often refers to the development of antibodies to non-ABO red blood cell (RBC) antigens following pregnancy, transfusion, or transplantation. The development of RBC alloantibodies can have important clinical consequences, particularly in patients who require chronic transfusions. It has been suggested that alloimmunization is more common in some clinical circumstances and patient populations than in others. As such, individuals that develop alloantibodies are frequently referred to as 'responders' in the medical literature. In contrast, individuals that do not develop alloantibodies despite repeated exposures to non-self blood group antigens have been referred to as 'non-responders'. The purpose of this article is to review the phenomenon of RBC alloimmunization in the context of responders and non-responders to: i) establish a basic framework for alloimmunization as reported across several diverse patient populations; ii) more fully explore literature reports which support the concept of responders/non-responders regarding blood group antigen alloimmunization; iii) summarize the mechanisms that have been shown to predispose an individual to alloimmunization to determine how these factors may differentiate 'responders' from 'non-responders'; and iv) briefly discuss some practical approaches to prevent alloimmunization in patients who may be prone to alloantibody development.

  10. Nonresponders to pharyngeal surgery for obstructive sleep apnea: insights from drug-induced sleep endoscopy.

    PubMed

    Kezirian, Eric J

    2011-06-01

    To examine drug-induced sleep endoscopy (DISE) findings in nonresponders to previous pharyngeal obstructive sleep apnea (OSA) surgery. Cross-sectional. DISE using propofol for unconscious sedation was performed in nonresponders to previous OSA surgery (including palate surgery with or without tonsillectomy and possible other procedures). Nonresponders were defined as subjects with a postoperative apnea-hypopnea index more than 10 events/hr. Recorded findings from DISE included the presence and degree of obstruction in the palatal and hypopharyngeal regions, the contributions of specific structures (velum, oropharyngeal lateral walls, tongue, and/or epiglottis) to upper airway obstruction, and the degree of mouth opening. Thirty-three nonresponders underwent DISE examinations. Age was 46.2 ± 11.8 years, and 9% (3 of 33) were female. On diagnostic sleep studies prior to DISE, the apnea-hypopnea index was 43.4 ± 26.6 events/hr. During DISE, a majority of subjects demonstrated residual palatal obstruction, and almost all demonstrated hypopharyngeal obstruction. A diversity of individual structures contributed to upper airway obstruction, often in combination. Moderate to severe mouth opening occurred in one-third of subjects and was associated with narrowing of upper airway dimensions. Residual upper airway obstruction in surgery nonresponders likely occurs due to multiple mechanisms, and DISE may enhance the understanding of them. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  11. Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

    PubMed Central

    Zielen, S.; Bühring, I.; Strnad, N.; Reichenbach, J.; Hofmann, D.

    2000-01-01

    There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 μg/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 μg/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients. PMID:10678957

  12. Postprocedure Mapping of Cardiac Resynchronization Lead Position Using Standard Fluoroscopy Systems: Implications for the Nonresponder with Scar

    PubMed Central

    PARKER, KATHERINE M.; BUNTING, ETHAN; MALHOTRA, ROHIT; CLARKE, SAMANTHA A.; MASON, PAMELA; DARBY, ANDREW E.; KRAMER, CHRISTOPHER M.; SALERNO, MICHAEL; HOLMES, JEFFREY W.; BILCHICK, KENNETH C.

    2014-01-01

    Background The relationship between cardiac resynchronization therapy (CRT), left ventricular (LV) lead position, scar, and regional mechanical function influences CRT response. Objective To determine LV lead position relative to LV structural characteristics in standard clinical practice, we developed and validated a practical yet mathematically rigorous method to register procedural fluoroscopic LV lead position with pre-CRT cardiac magnetic resonance (CMR). Methods After one-time calibration of the standard fluoroscopic suite, we identified the projected CMR LV lead position using three reference landmarks on both CMR and fluoroscopy. This predicted lead position was validated in a canine model by histology and in eight “validation group” patients based on postoperative computed tomography scans (n = 7) or CMR coronary sinus venography (n = 1). The methodology was applied in an additional eight patients with CRT nonresponse and infarction-related myocardial scar. Results The projected and actual lead positions were within 1.2 mm in the canine model. The median distance between projected and actual lead positions for the validation group (n = 8) and animal validation case was 11.3 mm (interquartile range 9.2–14.6 mm). In the application (nonresponder) group (n = 8), the lead mapped to the scar periphery in three patients, the core of the scar in one patient, and more than 3 cm from scar in four patients. Conclusions This methodology projects procedural fluoroscopic LV lead position onto pre-CRT CMR using standard fluoroscopic equipment and a one-time calibration, enabling assessment of LV lead position with sufficient accuracy to identify the lead position relative to regional function and infarction-related scar in CRT nonresponders. PMID:24472061

  13. Magnitude of visceral leishmaniasis and poor treatment outcome among HIV patients: meta-analysis and systematic review

    PubMed Central

    Alemayehu, Mekuriaw; Wubshet, Mamo; Mesfin, Nebiyu

    2016-01-01

    Background Visceral leishmaniasis (VL) coinfection with HIV/AIDS most often results in unfavorable responses to treatment, frequent relapses, and premature deaths. Scarce data are available, regarding the magnitude and poor treatment outcomes of VL-HIV coinfection. Objective The main objective of this systematic review was to describe the pooled prevalence of VL and poor treatment outcome among HIV patients. Review methods Electronic databases mainly PubMed were searched. Databases, such as Google and Google scholar, were searched for gray literature. Articles were selected based on their inclusion criterion, whether they included HIV-positive individuals with VL diagnosis. STATA 11 software was used to conduct a meta-analysis of pooled prevalence of VL-HIV coinfection. Results Fifteen of the 150 articles fulfilled the inclusion criteria. A majority of the study participants were males between 25 years and 41 years of age. The pooled prevalence of VL-HIV coinfection is 5.2% with 95% confidence interval of (2.45–10.99). Two studies demonstrated the impact of antiretroviral treatment on reduction in relapse rate compared with patients who did not start antiretroviral treatment. One study showed that the higher the baseline CD4+ cell count (>100 cells/mL) the lower the relapse rate. Former VL episodes were identified as risk factors for relapse in two articles. In one of the articles, an earlier bout of VL remains significant in the model adjusted to other variables. Conclusion The pooled prevalence of VL in HIV-infected patients is low and an earlier bout of VL and CD4+ count <100 cells/mL at the time of primary VL diagnosis are factors that predict poor treatment outcome. PMID:27042142

  14. Factors associated with mortality and default among patients with tuberculosis attending a teaching hospital clinic in Accra, Ghana.

    PubMed

    Burton, Nicole T; Forson, Audrey; Lurie, Mark N; Kudzawu, Samuel; Kwarteng, Ernest; Kwara, Awewura

    2011-12-01

    Tuberculosis (TB) remains a major cause of mortality despite availability of effective chemotherapy. This study was performed to identify contributing factors for poor outcome during anti-tuberculosis treatment at a teaching hospital chest clinic. Medical records of registered patients treated for TB between 1 January and 31 December, 2009 were reviewed and abstracted for demographic, clinical and outcome data. Risk factors for mortality during therapy were assessed using bivariate and multivariate logistics approaches. Of 599 patients, 355 (58.9%) completed therapy and/or were cured, 192 (32.1%) died, and 39 (6.5%) defaulted. In multivariate analysis, independent risk factors for mortality included pulmonary cases for which sputum smear status was unknown (odds ratio [OR] 13.7; 95% confidence interval [CI] 6.0, 31.4), HIV coinfection (OR, 3.6; 95% CI 2.4, 5.4), disseminated TB (OR, 2.2; 95% CI 1.0, 4.9), TB meningitis (OR, 2.8; 95% CI 1.5, 5.3), not having a treatment supporter (OR, 2.0; 95% CI 1.3, 3.1), and low body weight (OR, 11.0; 95% CI 3.1, 38.6). Not having a treatment supporter (OR, 3.2; 95% CI 1.6, 6.6) and HIV coinfection (OR, 2.4; 95% CI 1.2, 5.2) were also independently associated with treatment default. Our findings suggest that enhanced measures to reduce mortality and default in TB patients with HIV coinfection, disseminated or meningeal disease and those who have no treatment supporters may help improve treatment outcomes in Ghana.

  15. Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel.

    PubMed

    Soriano, Vincent; Puoti, Massimo; Peters, Marion; Benhamou, Yves; Sulkowski, Mark; Zoulim, Fabien; Mauss, Stefan; Rockstroh, Juergen

    2008-07-31

    Nearly 10% of the estimated 36 million people having HIV worldwide suffer from chronic hepatitis B virus (HBV) infection. The advent of new antiviral agents against HBV and the recent availability of improved molecular diagnostic tools have revolutioned the management of HIV/HBV coinfected patients. The present study represents an update of the current knowledge about HBV/HIV coinfection and an intent to provide practical advise about how to give the best care to HIV-infected persons with chronic hepatitis B.

  16. Human cysticercosis: antigens, antibodies and non-responders.

    PubMed Central

    Flisser, A; Woodhouse, E; Larralde, C

    1980-01-01

    Immunoelectrophoresis of sera from patients with brain cysticercosis against a crude antigenic extract from Cysticercus cellulosae indicates that nearly 50% of the patients do not make sufficient antibodies to ostensively precipitate. The other 50% of the patients who do make precipitating antibodies show a very heterogeneous response in the number of antigens they recognize as well as in the type of antigen--as classified by their electrophoretic mobilities. The most favoured, called antigen B, is recognized by 84% of positive sera and corresponds to one or a limited number of antigens isoelectric at pH 8.6. Indirect immunofluorescence with monospecific anti-human immunoglobulins, performed upon the immunoelectrophoretic preparations, reveal that all cysticercus antigens induced the synthesis of antibodies in the immunoglobulin classes in the order G greater than M greater than E greater than A greater than D. Finally, antigen H (an anodic component) seems to favour IgE relative to its ability to induce IgG. Thus, although in natural infection a good proportion of cysticercotic patients do not seem to mount an energetic antibody response against the parasite, giving rise to some speculations about immunosuppression, the fact that 50% do synthesize antibodies allows for some optimistic expectations from vaccination of humans--in view of the good results of vaccination in experimental animals mediated by IgG antibodies. A likely prospect for a human vaccine would be antigen B because it is the most frequently detected by humans, although its immunizing and toxic properties remain to be properly studied. Images FIG. 1 FIG. 3 FIG. 6 PMID:7389197

  17. Bacille-Calmette-Guerin non-responders: how to manage

    PubMed Central

    von Rundstedt, Friedrich-Carl

    2015-01-01

    Intravesical immunotherapy with bacille-Calmette-Guerin (BCG) is indicated in the treatment of high-risk and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Our goal is to describe the various disease states following induction and maintenance BCG and to describe contemporary treatment options and the current and projected clinical trial landscape for patients who recur following BCG therapy. PMID:26816828

  18. Understanding Faculty Survey Nonrespondents: Their Characteristics, Organizational Citizenship Behaviors, Workplace Attitudes, and Reasons for Nonparticipation

    ERIC Educational Resources Information Center

    Mathews, Kiernan Robert

    2013-01-01

    College and university administrators frequently survey their faculty to inform decisions affecting the academic workplace. Higher education researchers, too, rely heavily on survey methodologies in their scholarly work. Survey response rates, however, have been declining steadily for decades, and when nonrespondents and respondents systematically…

  19. Understanding Faculty Survey Nonrespondents: Their Characteristics, Organizational Citizenship Behaviors, Workplace Attitudes, and Reasons for Nonparticipation

    ERIC Educational Resources Information Center

    Mathews, Kiernan Robert

    2013-01-01

    College and university administrators frequently survey their faculty to inform decisions affecting the academic workplace. Higher education researchers, too, rely heavily on survey methodologies in their scholarly work. Survey response rates, however, have been declining steadily for decades, and when nonrespondents and respondents systematically…

  20. Nonresponders to pharyngeal surgery for obstructive sleep apnea: insights from drug-induced sleep endoscopy

    PubMed Central

    Kezirian, Eric J.

    2011-01-01

    Objectives/Hypothesis To examine DISE findings in nonresponders to previous pharyngeal OSA surgery Study Design cross-sectional Methods Drug-induced sleep endoscopy (DISE) using propofol for unconscious sedation was performed in nonresponders to previous OSA surgery (including palate surgery with or without tonsillectomy and possible other procedures), defined by an apnea-hypopnea index >10 events/hour. Recorded findings included the presence and degree of obstruction in the palatal and hypopharyngeal regions, the contributions of specific structures (velum, oropharyngeal lateral walls, tongue, and/or epiglottis) to upper airway obstruction, and the degree of mouth opening. Results Thirty-three nonresponders underwent DISE examinations. Age was 46.2±11.8 years, and 9% (3/33) were female. On diagnostic sleep studies prior to DISE, the apnea-hypopnea index was 43.4±26.6 events/hour. During DISE, a majority of subjects demonstrated residual palatal obstruction, and almost all demonstrated hypopharyngeal obstruction. A diversity of individual structures contributed to upper airway obstruction, often in combination. Moderate to severe mouth opening occurred in one-third of subjects and was associated with narrowing of upper airway dimensions. Conclusions Residual upper airway obstruction in surgery nonresponders likely occurs due to multiple mechanisms, and DISE may enhance the understanding of them. PMID:21557231

  1. Lithium response in bipolar disorder: No difference in GADL1 gene expression between cell lines from excellent-responders and non-responders.

    PubMed

    Moreira, Jeverson; Courtin, Cindie; Geoffroy, Pierre A; Curis, Emmanuel; Bellivier, Frank; Marie-Claire, Cynthia

    2017-05-01

    Previous association studies have shown mixed results between glutamic acid decarboxylase like-1 (GADL1) gene polymorphism and prophylactic lithium response in bipolar disorder (BD) patients. In the present study, GADL1 gene expression was investigated in regard to lithium response, using Alda scale, in lymphoblastoid cells (LCLs) of 36 Caucasian BD patients. No difference in GADL1 expression was observed among LCLs from excellent-responders, non-responders or controls. Furthermore, lithium did not induce significant changes in GADL1 expression levels after 4 or 8 days. These results did not support an association of GADL1 expression in the determination of a lithium response in BD patients.

  2. Do participants with low back pain who respond to spinal manipulative therapy differ biomechanically from nonresponders, untreated controls or asymptomatic controls?

    PubMed

    Wong, Arnold Y L; Parent, Eric C; Dhillon, Sukhvinder S; Prasad, Narasimha; Kawchuk, Gregory N

    2015-09-01

    Nonrandomized controlled study. To determine whether patients with low back pain (LBP) who respond to spinal manipulative therapy (SMT) differ biomechanically from nonresponders, untreated controls or asymptomatic controls. Some but not all patients with LBP report improvement in function after SMT. When compared with nonresponders, studies suggest that SMT responders demonstrate significant changes in spinal stiffness, muscle contraction, and disc diffusion. Unfortunately, the significance of these observations remains uncertain given methodological differences between studies including a lack of controls. Participants with LBP and asymptomatic controls attended 3 sessions for 7 days. On sessions 1 and 2, participants with LBP received SMT (+LBP/+SMT, n = 32) whereas asymptomatic controls did not (-LBP/-SMT, n = 57). In these sessions, spinal stiffness and multifidus thickness ratios were obtained before and after SMT and on day 7. Apparent diffusion coefficients from lumbar discs were obtained from +LBP/+SMT participants before and after SMT on session 1 and from an LBP control group that did not receive SMT (+LBP/-SMT, n = 16). +LBP/+SMT participants were dichotomized as responders/nonresponders on the basis of self-reported disability on day 7. A repeated measures analysis of covariance was used to compare apparent diffusion coefficients among responders, nonresponders, and +LBP/-SMT subjects, as well as spinal stiffness or multifidus thickness ratio among responders, nonresponders, and -LBP/-SMT subjects. After the first SMT, SMT responders displayed statistically significant decreases in spinal stiffness and increases in multifidus thickness ratio sustained for more than 7 days; these findings were not observed in other groups. Similarly, only SMT responders displayed significant post-SMT improvement in apparent diffusion coefficients. Those reporting post-SMT improvement in disability demonstrated simultaneous changes between self-reported and objective

  3. Treatment with telmisartan, a long-acting angiotensin II receptor blocker, prevents migraine attacks in Japanese non-responders to lomerizine.

    PubMed

    Ikeda, Ken; Hanashiro, Sayori; Ishikawa, Yuichi; Sawada, Masahiro; Kyuzen, Maya; Morioka, Harumi; Ebina, Junya; Nagasawa, Junpei; Yanagihashi, Masaru; Miura, Ken; Hirayama, Takehisa; Takazawa, Takanori; Kano, Osamu; Kawabe, Kiyokazu; Iwasaki, Yasuo

    2017-05-01

    Lomerizine, calcium channel blocker, is the most used medication for migraine prophylaxis in Japan. The effectiveness of this drug is reported as 50-75%. Telmisartan is angiotensin II receptor blockers which plasma half-life is 24 h. We examined whether telmisartan has preventative benefits in lomerizine non-responsive migraineurs. Lomerizine non-responders received telmisartan (20 mg/day) for 3 months after the investigation period of 3 months. Blood pressure, frequency of headache days/month, headache severity, and doses of triptans and analgesics were analyzed by Wilcoxon signed rank test. Thirty-three migraineurs (25 women and 8 men) participated in this study. Seven patients had migraine with aura and 26 patients had migraine without aura. Mean age (SD) was 46.6 (10.3) years. Mean duration (SD) of migraine was 20.4 (12.5) years. Headache severity exhibited mild degree in 5 patients, moderate degree in 9 patients and severe degree in 19 patients. Mean frequency (SD) of headache days was 10.9 (8.5) days/month. Mean usage (SD) of triptans was 4.8 (5.1) tablets/month and that of analgesics was 15.2 (22.2) tablets/month. Five patients (15%) had hypertension. Telmisartan administration had benefits in 30 patients (90%). This medication significantly decreased frequency of headache days (P < 0.01) and headache severity (P < 0.01). Doses of triptans were reduced at one-third (P < 0.05) and those of analgesia at one-fifth after telmisartan treatment (P < 0.01). After telmisartan, mean (SD) of systolic blood pressure was significantly decreased (P < 0.05). The present study supported that telmisartan treatment had preventive effects in 90% of lomerizine non-responders. Telmisartan non-responders (10%) exhibited chronic migraine and long migraine duration.

  4. S-adenosyl methionine (SAMe) augmentation of serotonin reuptake inhibitors for antidepressant nonresponders with major depressive disorder: a double-blind, randomized clinical trial.

    PubMed

    Papakostas, George I; Mischoulon, David; Shyu, Irene; Alpert, Jonathan E; Fava, Maurizio

    2010-08-01

    Despite the progressive increase in the number of antidepressants, many patients with major depressive disorder continue to be symptomatic. Clearly, there is an urgent need to develop better tolerated and more effective treatments for this disorder. The use of S-adenosyl methionine (SAMe), a naturally occurring molecule that serves as a methyl donor in human cellular metabolism, as adjunctive treatment for antidepressant nonresponders with major depressive disorder represents one such effort toward novel pharmacotherapy development. Participants were 73 serotonin reuptake inhibitor (SRI) nonresponders with major depressive disorder enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe (target dose: 800 mg/twice daily). Patients continued to receive their SRI treatment at a stable dose throughout the 6-week trial. The primary outcome measure for the study was the response rates according to the 17-item Hamilton Depression Rating Scale (HAM-D). The HAM-D response and remission rates were higher for patients treated with adjunctive SAMe (36.1% and 25.8%, respectively) than adjunctive placebo (17.6% versus 11.7%, respectively). The number needed to treat for response and remission was approximately one in six and one in seven, respectively. There was no statistically significant difference in the proportion of SAMe- versus placebo-treated patients who discontinued the trial for any reason (20.6% versus 29.5%, respectively), due to adverse events (5.1% versus 8.8%, respectively), or due to inefficacy (5.1% versus 11.7%, respectively). These preliminary results suggest that SAMe can be an effective, well-tolerated, and safe adjunctive treatment strategy for SRI nonresponders with major depressive disorder and warrant replication.

  5. Marital status, educational level and household income explain part of the excess mortality of survey non-respondents.

    PubMed

    Tolonen, Hanna; Laatikainen, Tiina; Helakorpi, Satu; Talala, Kirsi; Martelin, Tuija; Prättälä, Ritva

    2010-02-01

    Survey respondents and non-respondents differ in their demographic and socio-economic position. Many of the health behaviours are also known to be associated with socio-economic differences. We aimed to investigate how much of the excess mortality of survey non-respondents can be explained by the socio-economic differences between respondents and non-respondents. Questionnaire-based adult health behaviour surveys have been conducted in Finland annually since 1978. Data from the 1978 to 2002 surveys, including non-respondents, were linked with mortality data from the Finnish National Cause of Death statistics and with demographic and socio-economic register data (marital status, education and household income) obtained from Statistics Finland. The mortality follow-up lasted until 2006, in which period there were 12,762 deaths (7,994 in men and 4,768 in women) during the follow-up. Total and cause-specific mortality were higher among non-respondents in both men and women. Adjusting results for marital status, educational level and average household income decreased the excess total and cause-specific mortality of non-respondents in both men and women. Of the total excess mortality of non-respondents, 41% in men and 20% in women can be accounted for demographic and socio-economic factors. A part of the excess mortality among non-respondents can be accounted for their demographic and socio-economic characteristics. Based on these results we can assume that non-respondents tend to have more severe health problems, acute illnesses and unhealthy behaviours, such as smoking and excess alcohol use. These can be reasons for persons not taking part in population surveys.

  6. Hepatitis C virus reinfection after sustained virological response in HIV-infected patients with chronic hepatitis C.

    PubMed

    Pineda, Juan A; Núñez-Torres, Rocio; Téllez, Francisco; Mancebo, María; García, Federico; Merchante, Nicolás; Pérez-Pérez, Montserrat; Neukam, Karin; Macías, Juan; Real, Luis M

    2015-11-01

    To assess the incidence of hepatitis C virus (HCV) reinfections after therapy-induced clearance in HIV-coinfected patients with prior chronic hepatitis C. Eighty-four HIV-infected subjects, who had previously achieved sustained virological response (SVR) after being treated of chronic hepatitis C, were analyzed. In all of them, at least yearly HCV RNA determinations were carried out during a median (range) of 34 (12-146) months. Seventy-two (86%) subjects had been people who inject drugs (PWID), of whom 11 (15%) continued to use snorted or injected drugs during the follow-up. Four (4.76%) patients showed HCV reinfection (incidence 1.21 [95% confidence interval: 0.3-3.09] cases per 100 person-years). These patients maintained risk factors for HCV infection. In three cases, HCV genotype switched. Phylogenetic analysis of the remaining case suggested reinfection from his sexual partner. The incidence of HCV reinfection in the overall population of HIV-coinfected patients who achieved SVR after being treated against chronic hepatitis C is low. A low frequency of risk behavior is the main factor accounting for this modest rate of reinfection. The possibility of reinfection should not be considered a reason against treatment of HCV infection with direct acting antivirals in PWID. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  7. Participation in a mail survey: role of repeated mailings and characteristics of nonrespondents among recent mothers.

    PubMed

    Larroque, B; Kaminski, M; Bouvier-Colle, M H; Hollebecque, V

    1999-04-01

    This study analysed the characteristics of respondent and nonrespondent mothers at each stage of a survey procedure, from a initial questionnaire to a reminder letter and two repeated mailings. Of 938 mothers of liveborn children who, while maternity inpatients, received a questionnaire and information about a mail survey to follow 2 months later, 828 completed and returned the initial questionnaire, 708 agreed to participate in the mail survey and were sent the mail questionnaire, and 612 finally completed and returned the questionnaire at 2 months. There were differences between respondents and non-respondents for socio-demographic factors at each stage of the process. The final response rate to the mail questionnaire was higher among mothers who were younger, were breast feeding, and had more education, an occupation and fewer children. The characteristics of late respondents were intermediate between those of early to middle respondents and nonrespondents for age, educational level, breast feeding and occupation. Maternal and infant health varied only slightly according to response status. Repeated mailings increased response and diminished selection. A mail questionnaire after contact in a maternity ward is a cost-effective means of gathering data about a large sample of recent mothers and their children.

  8. Anxious Children and Adolescents Non-responding to CBT: Clinical Predictors and Families' Experiences of Therapy.

    PubMed

    Lundkvist-Houndoumadi, Irene; Thastum, Mikael

    2017-01-01

    The purpose of the study was to examine clinical predictors of non-response to manualized cognitive behaviour therapy (CBT) among youths (children and adolescents) with anxiety disorders, and to explore families' perspective on therapy, using a mixed methods approach. Non-response to manualized group CBT was determined among 106 youths of Danish ethnicity (7-17 years old) with a primary anxiety disorder, identified with the Clinical Global Impression of Improvement Scale at the 3-month follow-up. Twenty-four youths (22.6 %) had not responded to treatment, and a logistic regression analysis revealed that youths with a primary diagnosis of social phobia were seven times more likely not to respond, whereas youths with a comorbid mood disorder were almost four times more likely. Families of non-responding youths with primary social phobia and/or a comorbid mood disorder (n = 15) were interviewed, and data were analysed through interpretative phenomenological analysis. Two superordinate themes emerged: youths were not involved in therapy work, and manualized group format posed challenges to families. The mixed methods approach provided new perspectives on the difficulties that may be encountered by families of non-responding youths with a primary social phobia diagnosis and youths with a comorbid mood disorder during manualized group CBT. Clinical implications related to youths' clinical characteristics, and families' experience and suggestions are drawn. Copyright © 2015 John Wiley & Sons, Ltd. Youths with an anxiety disorder, who had a primary social phobia diagnosis and those, who had a comorbid mood disorder, were more likely not to respond to manualized group CBT. Parents of those non-responding youths often considered them as motivated to overcome their difficulties, but due to their symptomatology, they were unreceptive, reluctant and ambivalent and therefore not actively involved in therapy. The non-responding youths with social phobia felt evaluated and

  9. Peginterferon alfa-2b and ribavirin in thalassaemia/chronic hepatitis C virus-co-infected non-responder to standard interferon-based.

    PubMed

    Hamidah, A; Thambidorai, C R; Jamal, R

    2005-10-01

    We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.

  10. Antibody response to revaccination among adult non-responders to primary Hepatitis B vaccination in China.

    PubMed

    Zhang, Li; Liu, Jiaye; Lu, Jingjing; Yan, Bingyu; Song, Lizhi; Li, Li; Cui, Fuqiang; Zhang, Guomin; Wang, Fuzhen; Liang, Xiaofeng; Xu, Aiqiang

    2015-01-01

    About 10% adult failed to develop antibody response after primary hepatitis B vaccination, and revaccination may be an option to improve immune response, but the antibody responses to revaccination in adult non-responders have not been fully examined. Adult non-responders to primary 3-dose hepatitis B vaccination were randomly divided into 2 groups and revaccinated with 20 μg hepatitis B vaccine (HepB) derived from Saccharomyces Cerevisiae (HepB-SC) or 20 μg HepB derived from Chinese hamster ovary cells (HepB-CHO), respectively, at 0-, 1-, 6- month. Seroconversion rate and titer of antibody against hepatitis B surface antigen (anti-HBs) was measured one month after the 1st and 3rd revaccination dose. Anti-HBs seroconversion rates significantly increased from 54.98% [95% confidence interval (CI) 48.60%-61.24%] after the 1st revaccination dose to 89.24% (95% CI: 84.74%-92.79%) after the 3rd revaccination dose (P < 0.001), and the geometric mean titer (GMT) of anti-HBs increased from 12.18 mIU/ml (95%CI: 7.81-18.98 mIU/ml) to 208.31 mIU/ml (95% CI: 148.87-291.47 mIU/ml) (P = 0.008).Compared with those with anti-HBs titer <2 mIU/ml after primary vaccination, those with antibody titer ≥ 2 mIU/ml after primary vaccination had higher seroconversion rate after the 1st dose revaccination (38.36% vs. 78.10%, P < 0.001) and after the 3rd dose of revaccination (84.25% vs. 96.19%, P = 0.003), and had higher antibody titer after the 1st dose of revaccination (3.32 mIU/ml vs. 74.21 mIU/ml, P < 0.0001) and after the 3rd dose of revaccination (145.73 mIU/ml vs. 342.34 mIU/ml, P = 0.01). Anti-HBs titer was significantly higher in those revaccinated with HepB-CHO than those revaccinated with HepB-SC after the 3rd dose (131.46 mIU/ml vs. 313.38 mIU/ml, P = 0.01). Revaccination on adult HepB non-responders increased the immune response to HepB and may confer further protection against hepatitis B virus infection. If possible, revaccination might be an option to HepB non-responders

  11. Efficacy of sofosbuvir-based therapies in HIV/HCV infected patients and persons who inject drugs.

    PubMed

    Puoti, Massimo; Panzeri, Claudia; Rossotti, Roberto; Baiguera, Chiara

    2014-12-15

    In the era of Directly Acting anti HCV Antivirals treatment of hepatitis C is successful in the majority of persons treated. However, treatment of persons with HIV or who inject drugs remains challenging because of special issues: drug-drug interactions with antiretroviral, psychiatric and drug substitution therapies, treatment adherence, impact of treatment on HIV disease course or on risk of bacterial infections. Sofosbuvir induced sustained virologic response in 91% of 23 HIV/HCV coinfected persons treated in combination with ribavirin and pegylated interferon, in 83% of 497 treated in combination with ribavirin and in all 50 patients infected with HCV GT1 treated in combination with ledipasvir and ribavirin. The rates of efficacy in HCV-HIV coinfected were almost the same as those observed in HCV monoinfected suggesting that the efficacy of sofosbuvir is not reduced by HIV coinfection. There are no data on the efficacy of sofosbuvir in injection drugs users. The pangenotypic activity, the high barrier to resistance, the modest potential for drug-drug interactions makes sofosbuvir a reference drug for the treatment of these two special populations. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. All rights reserved.

  12. New use of an old drug: chloroquine reduces viral and ALT levels in HCV non-responders (a randomized, triple-blind, placebo-controlled pilot trial).

    PubMed

    Peymani, Payam; Yeganeh, Behzad; Sabour, Siamak; Geramizadeh, Bita; Fattahi, Mohammad Reza; Keyvani, Hossein; Azarpira, Negar; Coombs, Kevin M; Ghavami, Saied; Lankarani, Kamran B

    2016-06-01

    Hepatitis C virus (HCV) infection induces autophagy, but the virus assimilates the autophagic response into its own life cycle. Chloroquine (CQ) is an autophagy inhibitor that is clinically used to treat malaria. The aims of this pilot clinical trial were to evaluate the therapeutic potential and short-term safety of CQ in patients with chronic HCV genotype 1, who were unresponsive to a combination of pegylated interferon alpha and ribavirin. Ten non-responders to previous antiviral treatment(s) were randomized to receive either CQ (150 mg daily for 8 weeks) or placebo, and were followed for 4 weeks after CQ therapy. HCV RNA load and plasma alanine transaminase (ALT) levels were measured at baseline, week 4 (initial response), week 8 (end-of-treatment response), and at the end of 12 weeks. A significant decrease in HCV RNA after the treatments (week 8) was observed in all patients in the CQ group (P = 0.04). However, HCV RNA levels increased within 4 weeks after discontinuation of CQ treatment although they were still lower than baseline. In addition, the ALT normalized during treatment in the CQ group. However, this response was also lost after treatment cessation. This study provides preliminary evidence that CQ is possibly a safe treatment option for HCV non-responders.

  13. Comparative Proteomic Analysis of Advanced Ovarian Cancer Tissue to Identify Potential Biomarkers of Responders and Nonresponders to First-Line Chemotherapy of Carboplatin and Paclitaxel

    PubMed Central

    Sehrawat, Urmila; Pokhriyal, Ruchika; Gupta, Ashish Kumar; Hariprasad, Roopa; Khan, Mohd Imran; Gupta, Divya; Naru, Jasmine; Singh, Sundararajan Baskar; Mohanty, Ashok Kumar; Vanamail, Perumal; Kumar, Lalit; Kumar, Sunesh; Hariprasad, Gururao

    2016-01-01

    Conventional treatment for advanced ovarian cancer is an initial debulking surgery followed by chemotherapy combination of carboplatin and paclitaxel. Despite initial high response, three-fourths of these women experience disease recurrence with a dismal prognosis. Patients with advanced-stage ovarian cancer who underwent cytoreductive surgery were enrolled and tissue samples were collected. Post surgery, these patients were started on chemotherapy and followed up till the end of the cycle. Fluorescence-based differential in-gel expression coupled with mass spectrometric analysis was used for discovery phase of experiments, and real-time polymerase chain reaction, Western blotting, and pathway analysis were performed for expression and functional validation of differentially expressed proteins. While aldehyde reductase, hnRNP, cyclophilin A, heat shock protein-27, and actin are upregulated in responders, prohibitin, enoyl-coA hydratase, peroxiredoxin, and fibrin-β are upregulated in the nonresponders. The expressions of some of these proteins correlated with increased apoptotic activity in responders and decreased apoptotic activity in nonresponders. Therefore, the proteins qualify as potential biomarkers to predict chemotherapy response. PMID:26997873

  14. A comparison of physical and psychological features of responders and non-responders to cervical facet blocks in chronic whiplash

    PubMed Central

    2013-01-01

    Background Cervical facet block (FB) procedures are often used as a diagnostic precursor to radiofrequency neurotomies (RFN) in the management of chronic whiplash associated disorders (WAD). Some individuals will respond to the FB procedures and others will not respond. Such responders and non-responders provided a sample of convenience to question whether there were differences in their physical and psychological features. This information may inform future predictive studies and ultimately the clinical selection of patients for FB procedures. Methods This cross-sectional study involved 58 individuals with chronic WAD who responded to cervical FB procedures (WAD_R); 32 who did not respond (WAD_NR) and 30 Healthy Controls (HC)s. Measures included: quantitative sensory tests (pressure; thermal pain thresholds; brachial plexus provocation test); nociceptive flexion reflex (NFR); motor function (cervical range of movement (ROM); activity of the superficial neck flexors during the cranio-cervical flexion test (CCFT). Self-reported measures were gained from the following questionnaires: neuropathic pain (s-LANSS); psychological distress (General Health Questionnaire-28), post-traumatic stress (PDS) and pain catastrophization (PCS). Individuals with chronic whiplash attended the laboratory once the effects of the blocks had abated and symptoms had returned. Results Following FB procedures, both WAD groups demonstrated generalized hypersensitivity to all sensory tests, decreased neck ROM and increased superficial muscle activity with the CCFT compared to controls (p < 0.05). There were no significant differences between WAD groups (all p > 0.05). Both WAD groups demonstrated psychological distress (GHQ-28; p < 0.05), moderate post-traumatic stress symptoms and pain catastrophization. The WAD_NR group also demonstrated increased medication intake and elevated PCS scores compared to the WAD_R group (p < 0.05). Conclusions Chronic WAD responders and non-responders to FB

  15. Legionella pneumophila infection presenting as headache, confusion and dysarthria in a human immunodeficiency virus-1 (HIV-1) positive patient: case report.

    PubMed

    Robbins, Nathaniel M; Kumar, Aditi; Blair, Barbra M

    2012-09-22

    Legionella pneumophila is a common cause of community-acquired pneumonia. Central nervous system dysfunction is common, and diagnosis in the absence of pulmonary symptoms can be challenging. Here we describe an atypical clinical presentation of Legionella infection in a patient with HIV who was found to have an unusual neuroradiologic lesion that further served to obscure the diagnosis. This is the first such description in a patient with Legionellosis and HIV coinfection. A 43 year-old HIV positive man presented to our hospital with dysarthria, fevers, headache, and altered mental status. Initial work-up revealed pneumonia and a lesion of the splenium of the corpus callosum on magnetic resonance imaging. He was subsequently diagnosed with Legionella pneumonia and treated with complete symptom resolution. Neurologic abnormalities are frequent in Legionellosis, but the diagnosis may be difficult in the absence of overt respiratory symptoms and in the presence of HIV coinfection. A high index of suspicion and early initiation of empiric antibiotics is imperative since early treatment may help prevent long-term sequelae. Neuroimaging abnormalities, though rare, can help the physician narrow down the diagnosis and avoid unnecessary invasive testing. Future studies should aim to elucidate the as yet unknown role of neuroimaging in the diagnoses and prognostication of Legionellosis, as well as the interaction between Legionella infection and HIV.

  16. Examining non-response bias in substance use research--are late respondents proxies for non-respondents?

    PubMed

    Studer, Joseph; Baggio, Stéphanie; Mohler-Kuo, Meichun; Dermota, Petra; Gaume, Jacques; Bertholet, Nicolas; Daeppen, Jean-Bernard; Gmel, Gerhard

    2013-09-01

    Non-response is a major concern among substance use epidemiologists. When differences exist between respondents and non-respondents, survey estimates may be biased. Therefore, researchers have developed time-consuming strategies to convert non-respondents to respondents. The present study examines whether late respondents (converted former non-participants) differ from early respondents, non-consenters or silent refusers (consent givers but non-participants) in a cohort study, and whether non-response bias can be reduced by converting former non-respondents. 6099 French- and 5720 German-speaking Swiss 20-year-old males (more than 94% of the source population) completed a short questionnaire on substance use outcomes and socio-demographics, independent of any further participation in a cohort study. Early respondents were those participating in the cohort study after standard recruitment procedures. Late respondents were non-respondents that were converted through individual encouraging telephone contact. Early respondents, non-consenters and silent refusers were compared to late respondents using logistic regressions. Relative non-response biases for early respondents only, for respondents only (early and late) and for consenters (respondents and silent refusers) were also computed. Late respondents showed generally higher patterns of substance use than did early respondents, but lower patterns than did non-consenters and silent refusers. Converting initial non-respondents to respondents reduced the non-response bias, which might be further reduced if silent refusers were converted to respondents. Efforts to convert refusers are effective in reducing non-response bias. However, converted late respondents cannot be seen as proxies of non-respondents, and are at best only indicative of existing response bias due to persistent non-respondents. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. What is wrong with non-respondents? Alcohol-, drug- and smoking-related mortality and morbidity in a 12-year follow-up study of respondents and non-respondents in the Danish Health and Morbidity Survey.

    PubMed

    Christensen, Anne Illemann; Ekholm, Ola; Gray, Linsay; Glümer, Charlotte; Juel, Knud

    2015-09-01

    Response rates in health surveys have diminished over the last two decades, making it difficult to obtain reliable information on health and health-related risk factors in different population groups. This study compared cause-specific mortality and morbidity among survey respondents and different types of non-respondents to estimate alcohol-, drug- and smoking-related mortality and morbidity among non-respondents. Prospective follow-up study of respondents and non-respondents in two cross-sectional health surveys. Denmark. A total sample of 39 540 Danish citizens aged 16 years or older. Register-based information on cause-specific mortality and morbidity at the individual level was obtained for respondents (n = 28 072) and different types of non-respondents (refusals n = 8954; illness/disabled n = 731, uncontactable n = 1593). Cox proportional hazards models were used to examine differences in alcohol-, drug- and smoking-related mortality and morbidity, respectively, in a 12-year follow-up period. Overall, non-response was associated with a significantly increased hazard ratio (HR) of 1.56 [95% confidence interval (CI) = 1.36-1.78] for alcohol-related morbidity, 1.88 (95% CI = 1.38-2.57) for alcohol-related mortality, 1.55 (95% CI = 1.27-1.88) for drug-related morbidity, 3.04 (95% CI = 1.57-5.89) for drug-related mortality and 1.15 (95% CI = 1.03-1.29) for smoking-related morbidity. The hazard ratio for smoking-related mortality also tended to be higher among non-respondents compared with respondents, although no significant association was evident (HR = 1.14; 95% CI = 0.95-1.36). Uncontactable and ill/disabled non-respondents generally had a higher hazard ratio of alcohol-, drug- and smoking-related mortality and morbidity compared with refusal non-respondents. Health survey non-respondents in Denmark have an increased hazard ratio of alcohol-, drug- and smoking-related mortality and morbidity compared with

  18. Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment.

    PubMed

    Walkup, John T; Wagner, Karen Dineen; Miller, Leslie; Yenokyan, Gayane; Luby, Joan L; Joshi, Paramjit T; Axelson, David A; Robb, Adelaide; Salpekar, Jay A; Wolf, Dwight; Sanyal, Abanti; Birmaher, Boris; Vitiello, Benedetto; Riddle, Mark A

    2015-12-01

    The Treatment of Early Age Mania (TEAM) study evaluated lithium, risperidone, and divalproex sodium (divalproex) in children with bipolar I disorder who were naive to antimanic medication, or were partial or nonresponders to 1 of 3 study medications. This report evaluates the benefit of either an add-on or a switch of antimanic medications for an 8-week trial period in partial responders and nonresponders, respectively. TEAM is a randomized, controlled trial of individuals (N = 379) aged 6 to 15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (mixed or manic phase). Participants (n = 154) in this report were either nonresponders or partial responders to 1 of the 3 study medications. Nonresponders (n = 89) were randomly assigned to 1 of the other 2 antimanic medications and cross-tapered. Partial responders (n = 65) were randomly assigned to 1 of 2 other antimanic medications as an add-on to their initial medication. Adverse event (AE) rates are reported only for the add-on group. Response rate for children switched to risperidone (47.6%) was higher than for those switched to either lithium (12.8%; p = .005; number needed to treat [NNT] = 3; 95% CI = 1.71-9.09) or divalproex (17.2%; p = .03; NNT = 3; 95% CI = 1.79-20.10); response rate for partial responders who added risperidone (53.3%) was higher than for those who added divalproex (0%; p = .0002; NNT = 2; 95% CI = 1.27-3.56) and trended higher for lithium (26.7%; p = .07; NNT = 4). Reported AEs in the add-on group were largely consistent with the known AE profile for the second medication. Weight gain (kg) was observed for all add-on medications: lithium add-on (n = 29 of 30) = 1.66 ± 1.97; risperidone add-on (n = 15 of 15) = 2.8 ± 1.34; divalproex add-on (n = 19 of 20) = 1.42 ± 1.96. There was no evidence at the 5% significance level that the average weight gain was different by study medication for partial responders (p = .07, 1-way analysis of variance

  19. Characterization of clinical and immunological features in patients coinfected with dengue virus and HIV.

    PubMed

    Torrentes-Carvalho, Amanda; Hottz, Eugênio Damaceno; Marinho, Cintia Ferreira; da Silva, Jéssica Badolato-Corrêa; Pinto, Luzia Maria de Oliveira; Fialho, Luciana Gomes; Bozza, Fernando Augusto; Cunha, Rivaldo Venâncio; Damasco, Paulo Vieira; Kubelka, Claire Fernandes; de Azeredo, Elzinandes Leal

    2016-03-01

    The pathogenesis of dengue in subjects coinfected with HIV remains largely unknown. We investigate clinical and immunological parameters in coinfected DENV/HIV patients. According to the new dengue classification, most coinfected DENV/HIV patients presented mild clinical manifestations of dengue infection. Herein, we show that DENV/HIV coinfected patients had higher CD8 T cells percentages reflected as a lower CD4/CD8 ratio. Furthermore, CCR5 expression on CD4 T cells and CD107a expression on both T subsets were significantly higher in coinfected patients when compared with monoinfected DENV and HIV individuals respectively. Increased inflammatory response was observed in treated HAART coinfected patients despite undetectable HIV load. These data indicate that DENV infection may influence the clinical profile and immune response in individuals concomitantly infected with HIV.

  20. The Auditory P3 in Antidepressant Pharmacotherapy Treatment Responders, Non-Responders and Controls

    PubMed Central

    Jaworska, Natalia; De Somma, Elisea; Blondeau, Claude; Tessier, Pierre; Norris, Sandhaya; Fusee, Wendy; Smith, Dylan; Blier, Pierre; Knott, Verner

    2013-01-01

    Event-related potentials (ERPs), derived from electroencephalographic (EEG) recordings, can index electrocortical activity related to cognitive operations. The fronto-central P3a ERP is involved in involuntary processing of novel auditory information, whereas the parietal P3b indexes controlled attention processing. The amplitude of the auditory P3b has been found to be decreased in major depressive disorder (MDD). However, few studies have examined the relationship between the P3b, the related P3a, and antidepressant treatment response. We tested 53 unmedicated individuals (25 females) with MDD as well as 43 non-depressed controls (23 females) on the novelty oddball task, wherein infrequent deviant (target) and frequent standard (non-target) tones were presented, along with infrequent novel (non-target/distractor) sounds. The P3a and P3b ERPs were assessed to the novel and target sounds, respectively, as were accompanying behavioural performance measures. Depression ratings and antidepressant response status were assessed following 12 weeks of pharmacotherapy with three different regimens. Antidepressant treatment non-responders had smaller baseline P3a/b amplitudes than responders and healthy controls. Baseline P3b amplitude also weakly predicted the extent of depression rating changes by week 12. Females exhibited larger P3a/b amplitudes than males. With respect to task performance, controls had more target hits than treatment non-responders. ERP measures correlated with clinical changes in males and with behavioural measures in females. These results suggest that greater (or control-like) baseline P3a/b amplitudes are associated with a positive antidepressant response, and that gender differences characterize the P3 and, hence, basic attentive processes. PMID:23664712

  1. [Bias due to non-responders in an epidemiological study (SAPALDIA)].

    PubMed

    Luthi, J C; Zellweger, J P; Grize, L; Leuenberger, P; Ackermann-Liebrich, U

    1997-01-01

    Within the Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) 16267 adults aged 18 to 60 years from 8 different locations in Switzerland were randomly selected for answering a questionnaire about respiratory health and have a lung function examination with allergy test. 9561 subjects agreed with the examination (59%) (= responders, R). In order to study the possible influence of the bias introduced by non-responders (NR), 221 subjects who refused to participate among the 966 first subjects selected in Payerne were contacted by phone. 142 accepted a home visit and answered a shortened questionnaire about the main respiratory symptoms and diseases and indicated furthermore the reasons for their refusal. Non-responders have a lower mean educational level and belong to lower social classes than responders. The frequency of respiratory symptoms and diseases, allergies and smoking is similar in R and NR except a higher frequency of wheezing during the last 12 month (R: 12.5%, NR: 5.6%, p = 0.03). The level of carbon monoxide in expired air is higher in NR (17.6 ppm) that in R (11.9 ppm) (p = 0.01). A similar difference exists between NR (30.7 pp) and R (24.8 ppm) among current smokers (p < 0.01). The main reasons for refusal are lack of time (27.5%), lack of interest for medical study (22.6%), fear of health professionals (18.3%) or the existence of a another disease (9.9%). Furthermore, 2.8% of the subjects consider a medical study as useless and refuse principally any participation. The role of local press and media in the decision to participate seems to be important. Globally, the differences between R and NR are minimal and should not influence the validity of the results of the SAPALDIA study.

  2. MORBIDITY AND MORTALITY PROFILE OF HIV INFECTED PATIENTS, WITH AND WITHOUT HEPATITIS C COINFECTION

    PubMed Central

    Mayor, Angel M.; Gomez, Maria A.; Fernandez, Diana M.; Rios-Olivares, Eddy; Thomas, James C.; Hunter, Robert F.

    2014-01-01

    Purpose Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) coinfection is an important and frequent scenario, predominantly in injecting drug users (IDUs). The present study evaluated morbidity and mortality variation in HIV infected patients with and without HCV coinfection. Methods Coinfection prevalence was determined in 356 HIV infected persons. Their clinical manifestations, laboratory findings, risk factors, HIV therapies and mortality rates were evaluated. Results HCV prevalence was 54% in the overall group and 81% in IDUs, with predominance of HCV genotype 1. Mortality rates were similar in patients with and without coinfection; however coinfected patients had significantly higher liver damage as a cause of mortality when compared with those who were not coinfected. Conclusions The high HCV prevalence and the emerging mortality from liver diseases, revealed the significance of this coinfection in HIV epidemic. Primary and secondary prevention are necessary to reduce the expanding impact of HCV infection in HIV patients. PMID:16474077

  3. Adult separation anxiety in treatment nonresponders with anxiety disorders: delineation of the syndrome and exploration of attachment-based psychotherapy and biomarkers.

    PubMed

    Milrod, Barbara; Altemus, Margaret; Gross, Charles; Busch, Fredric; Silver, Gabrielle; Christos, Paul; Stieber, Joshua; Schneier, Franklin

    2016-04-01

    Clinically significant separation anxiety [SA] has been identified as being common among patients who do not respond to psychiatric interventions, regardless of intervention type (pharmacological or psychotherapeutic), across anxiety and mood disorders. An attachment formation and maintenance domain has been proposed as contributing to anxiety disorders. We therefore directly determined prevalence of SA in a population of adult treatment non-responders suffering from primary anxiety. In these separation anxious nonresponders, we pilot-tested an SA-focused, attachment-based psychotherapy for anxiety, Panic-Focused Psychodynamic Psychotherapy-eXtended Range [PFPP-XR], and assessed whether hypothesized biomarkers of attachment were engaged. We studied separation anxiety [SA] in 46 adults (ages 23-70 [mean 43.9 (14.9)]) with clinically significant anxiety symptoms (Hamilton Anxiety Rating Scale [HARS]≥15), and reporting a history of past non-response to psychotherapy and/or medication treatments. Thirty-seven (80%) had clinically significant symptoms of separation anxiety (Structured Clinical Interview for Separation Anxiety Symptoms [SCI-SAS] score≥8). Five of these subjects completed an open clinical trial of Panic Focused Psychodynamic Psychotherapy eXtended Range [PFPP-XR], a 21-24 session, 12-week manualized attachment-focused anxiolytic psychodynamic psychotherapy for anxiety. Patients improved on "adult threshold" SCI-SAS (current separation anxiety) (p=.016), HARS (p=0.002), and global severity, assessed by the Clinical Global Impression Scale (p=.0006), at treatment termination. Salivary oxytocin levels decreased 67% after treatment (p=.12). There was no significant change in high or low frequency HRV after treatment, but change in high frequency HRV inversely correlated with treatment change in oxytocin (p<.02), and change in low frequency HRV was positively associated with change in oxytocin (p<.02). SA is surprisingly prevalent among non-responders to

  4. Factors Related to Outcome in a School-Based Intensive Mental Health Program: An Examination of Nonresponders

    ERIC Educational Resources Information Center

    Jacobs, Anne K.; Roberts, Michael C.; Vernberg, Eric M.; Nyre, Joseph E.; Randall, Camille J.; Puddy, Richard W.

    2008-01-01

    We examined factors related to treatment responders (n = 35) and nonresponders (n = 16) in a group of 51 children admitted to the Intensive Mental Health Program (IMHP). Children's response to treatment was coded based on their functioning at intake and discharge using total CAFAS scores. Demographic variables, length of treatment, number of…

  5. Factors Related to Outcome in a School-Based Intensive Mental Health Program: An Examination of Nonresponders

    ERIC Educational Resources Information Center

    Jacobs, Anne K.; Roberts, Michael C.; Vernberg, Eric M.; Nyre, Joseph E.; Randall, Camille J.; Puddy, Richard W.

    2008-01-01

    We examined factors related to treatment responders (n = 35) and nonresponders (n = 16) in a group of 51 children admitted to the Intensive Mental Health Program (IMHP). Children's response to treatment was coded based on their functioning at intake and discharge using total CAFAS scores. Demographic variables, length of treatment, number of…

  6. Stopping rules for surveys with multiple waves of nonrespondent follow-up.

    PubMed

    Rao, R Sowmya; Glickman, Mark E; Glynn, Robert J

    2008-05-30

    In surveys with multiple waves of follow-up, nonrespondents to the first wave are sometimes followed intensively but this does not guarantee an increase in the response rate or an appreciable change in the estimate of interest. Most prior research has focused on stopping rules for Phase I clinical trials. To our knowledge there are no standard methods to stop follow-up in observational studies. Previous research suggests optimal stopping strategies where decisions are based on achieving a given precision for minimum cost or reducing cost for a given precision. In this paper, we propose three stopping rules that are based on assessing whether successive waves of sampling provide evidence that the parameter of interest is changing. Two of the rules rely on examining patterns of observed responses while the third rule uses missing data methods to multiply impute missing responses. We also present results from a simulation study to evaluate our proposed methods. Our simulations suggest that rules that adjust for nonresponse are preferred for decisions to discontinue follow-up since they reduce bias in the estimate of interest. The rules are not complicated and may be applied in a straightforward manner. Discontinuing follow-up would save time and possibly resources, and adjusting for the nonresponse in the analysis would reduce the impact of nonresponse bias.

  7. Constraints of nonresponding flows based on cross layers in the networks

    NASA Astrophysics Data System (ADS)

    Zhou, Zhi-Chao; Xiao, Yang; Wang, Dong

    2016-02-01

    In the active queue management (AQM) scheme, core routers cannot manage and constrain user datagram protocol (UDP) data flows by the sliding window control mechanism in the transport layer due to the nonresponsive nature of such traffic flows. However, the UDP traffics occupy a large part of the network service nowadays which brings a great challenge to the stability of the more and more complex networks. To solve the uncontrollable problem, this paper proposes a cross layers random early detection (CLRED) scheme, which can control the nonresponding UDP-like flows rate effectively when congestion occurs in the access point (AP). The CLRED makes use of the MAC frame acknowledgement (ACK) transmitting congestion information to the sources nodes and utilizes the back-off windows of the MAC layer throttling data rate. Consequently, the UDP-like flows data rate can be restrained timely by the sources nodes in order to alleviate congestion in the complex networks. The proposed CLRED can constrain the nonresponsive flows availably and make the communication expedite, so that the network can sustain stable. The simulation results of network simulator-2 (NS2) verify the proposed CLRED scheme.

  8. Long-term follow-up of previous hepatitis C virus positive nonresponders to interferon monotherapy successfully retreated with combination therapy: are they really cured?

    PubMed

    Ciancio, Alessia; Smedile, Antonina; Giordanino, Chiara; Colletta, Cosimo; Croce, Guido; Pozzi, Massimo; Cariti, Giuseppe; Macor, Antonio; Biglino, Alberto; Di Napoli, Angelo; Tappero, Gian Franco; Andreoni, Massimo; Manca, Aldo; Prandi, Giancarlo; Calleri, Guido; Orsi, Pier Giulio; Ciccone, Giovannino; Rizzetto, Mario; Saracco, Giorgio

    2006-08-01

    To evaluate whether in chronic hepatitis C-positive patients who failed to respond to interferon (IFN) monotherapy a sustained response obtained with retreatment using the combination therapy of IFN + ribavirin can be safely considered to reflect eradication of the infection. Prospective follow-up of a cohort of 97 patients who responded to retreatment with different regimens of IFN + ribavirin after failing to respond to a first IFN monotherapy course. The patients were followed throughout 7 yr of follow-up with determinations of HCV viremia every 6 months. At the end of the follow-up, 11 patients (11.3%) showed a viremic reappearance. HCV late relapse rates were 0%, 13%, 20%, and 12% in patients retreated, respectively, with 3 MU IFN + ribavirin for 12 months (Group 1), 5 MU IFN + ribavirin for 12 months (Group 2), 3 MU IFN + ribavirin for 6 months (Group 3), and 5 MU IFN + ribavirin for 6 months (Group 4) (Group 2 vs Group 3, p= 0.005). The virologic relapses occurred within 2 yr from therapy withdrawal. Among patients with genotype 1 and 4, the long-term response was significantly higher in Group 2 than in Group 3 (15%vs 3%, p= 0.03). In patients with genotype 2 and 3, the long-term virological response was not affected by the different regimens. Nonresponders to IFN monotherapy who achieve a sustained virologic response after retreatment with IFN + ribavirin stand a discrete risk of HCV reactivation within 2 yr after therapy.

  9. Hansen's disease and HIV coinfection with facial nerve palsy.

    PubMed

    Yadav, Nidhi; Kar, Sumit; Madke, Bhushan; Gangane, Nitin

    2015-01-01

    There are very few published reports of HIV leprosy co infection in India in spite of having a large burden of both leprosy and HIV. Herein we are reporting a case of co-infection of Hansen's disease and HIV with facial nerve palsy.

  10. Experimental systems for studying Plasmodium/HIV coinfection.

    PubMed

    Frischknecht, Friedrich; Fackler, Oliver T

    2016-07-01

    Coinfections with Human Immunodeficiency Virus (HIV) and Plasmodium, the causative agents of AIDS and malaria, respectively, are frequent and their comorbidity especially in sub-Saharan Africa is high. While clinical studies suggest an influence of the two pathogens on the outcome of the respective infections, experimental studies on the molecular and immunological impact of coinfections are rare. This reflects the limited availability of suitable model systems that reproduce key properties of both pathologies. Here, we discuss key aspects of coinfection with a focus on currently established experimental systems, their limitations for coinfection studies and potential strategies for their improvement.

  11. The cursed duet today: Tuberculosis and HIV-coinfection.

    PubMed

    Tiberi, Simon; Carvalho, Anna Cristina C; Sulis, Giorgia; Vaghela, Devan; Rendon, Adrian; Mello, Fernanda C de Q; Rahman, Ananna; Matin, Nashaba; Zumla, Ali; Pontali, Emanuele

    2017-03-01

    The tuberculosis (TB) and HIV syndemic continues to rage and are a major public health concern worldwide. This deadly association raises complexity and represent a significant barrier towards TB elimination. TB continues to be the leading cause of death amongst HIV-infected people. This paper reports the challenges that lay ahead and outlines some of the current and future strategies that may be able to address this co-epidemic efficiently. Improved diagnostics, cheaper and more effective drugs, shorter treatment regimens for both drug-sensitive and drug-resistant TB are discussed. Also, special topics on drug interactions, TB-IRIS and TB relapse are also described. Notwithstanding the defeats and meagre investments, diagnosis and management of the two diseases have seen significant and unexpected improvements of late. On the HIV side, expansion of ART coverage, development of new updated guidelines aimed at the universal treatment of those infected, and the increasing availability of newer, more efficacious and less toxic drugs are an essential element to controlling the two epidemics. On the TB side, diagnosis of MDR-TB is becoming easier and faster thanks to the new PCR-based technologies, new anti-TB drugs active against both sensitive and resistant strains (i.e. bedaquiline and delamanid) have been developed and a few more are in the pipeline, new regimens (cheaper, shorter and/or more effective) have been introduced (such as the "Bangladesh regimen") or are being tested for MDR-TB and drug-sensitive-TB. However, still more resources will be required to implement an integrated approach, install new diagnostic tests, and develop simpler and shorter treatment regimens.

  12. Long-Term Effect of Rifampicin-Based Anti-TB Regimen Coadministration on the Pharmacokinetic Parameters of Efavirenz and 8-Hydroxy-Efavirenz in Ethiopian Patients.

    PubMed

    Habtewold, Abiy; Aklillu, Eleni; Makonnen, Eyasu; Amogne, Wondwossen; Yimer, Getnet; Aderaye, Getachew; Bertilsson, Leif; Owen, Joel S; Burhenne, Jürgen

    2016-12-01

    We compared the pharmacokinetic (PK) exposure parameters of efavirenz (EFV) and its major inactive metabolite, 8-hydroxy-efavirenz (8-OH-EFV), in an open-label, single-sequence, and parallel design of HIV-infected and tuberculosis (TB)-HIV-coinfected Ethiopian patients in the HIV-TB Pharmagene study with 20 and 33 patients, respectively. Both treatment groups underwent PK sampling following oral 600 mg EFV in week 16 of initiating EFV-based combination antiretroviral therapy. The TB-HIV-coinfected group repeated the PK sampling 8 weeks after stopping rifampin (RIF)-based anti-TB treatment. Between-treatment group analysis indicated no significant effect of RIF-based anti-TB cotreatment on PK exposure parameters of EFV, nor was there a significant effect after controlling for sex or CYP2B6 genotype. However, RIF-based therapy in TB-HIV-coinfected patients had significantly increased 8-OH-EFV PK exposure measures and metabolic ratio relative to HIV-only patients, AUC0-24 greater by 79%. The effect was more prominent in women and CYP2B6*6 carriers in within-sex and CYP2B6 genotype comparisons. Within-subject comparisons for AUC0-24 and Cmax when "on" and "off" RIF-based anti-TB cotreatment showed geometric mean ratios (90% confidence intervals) of 100.5% (98.7%-102.3%) and 100.2% (98.1%-102.4%), respectively, for EFV and 98.6% (95.5%-101.7%-) and 97.6% (92.2%-103.0%), respectively, for 8-OH-EFV. We report no significant influence of RIF-based anti-TB cotherapy on the EFV PK exposure measures. The study also calls for caution related to higher exposure to 8-OH-EFV during simultaneous coadministration of EFV and RIF-based anti-TB regimens, which may be associated with neurotoxicity, particularly in female patients and CYP2B6*6 carriers. © 2016, The American College of Clinical Pharmacology.

  13. Liver fibrosis progression is related to CD4 cell depletion in patients coinfected with hepatitis C virus and human immunodeficiency virus.

    PubMed

    Puoti, M; Bonacini, M; Spinetti, A; Putzolu, V; Govindarajan, S; Zaltron, S; Favret, M; Callea, F; Gargiulo, F; Donato, F; Carosi, G

    2001-01-01

    A total of 204 patients with liver biopsy-proven hepatitis C virus (HCV) infection, 84 with and 120 without human immunodeficiency virus (HIV) coinfection, were studied, to evaluate variables possibly associated with the stage of liver fibrosis. All patients were injection drugs users, with a mean age of 32 years and an estimated duration of HCV infection of 12 years. Twenty-four patients (11%) had many fibrous septa with (5%) or without (6%) cirrhosis, 56 (27%) had few fibrous septa, and 124 (60%) had no fibrous septa. In all patients, an association was found between CD4 cell counts <500 cells/mm(3)and the presence of many fibrous septa (odds ratio, 3.2; P=.037), independent of HIV infection and other factors. These results suggest that HIV infection-induced CD4 depletion is independently associated with the severity of liver fibrosis in chronic HCV infection.

  14. Immune response to second vaccination series of hepatitis B virus among booster dose non-responders.

    PubMed

    Salama, Iman I; Sami, Samia M; Salama, Somaia I; Rabah, Thanaa Mahmoud; El Etreby, Lobna Ahmed; Abdel Hamid, Amany T; Elmosalami, Dalia; El Hariri, Hazem; Said, Zeinab N

    2016-04-07

    To evaluate the response to second vaccination series among post-booster sero-negative children who had previously received compulsory HBV vaccination. After given a booster dose to 1070 children, 103 of them failed to generate anamnestic response (anti-HBs <10 IU/L). Only 91/103 children received additional two doses of recombinant HBV vaccine (i.e. 2(nd) vaccination series) after 1 and 6 months post-booster. Blood sample was withdrawn aseptically one month later for quantitative assessment of anti-HBs to detect development of protective immune response (≥10 IU/L). Immunological vaccination failure was assigned to children who did not develop protective immune response after 2(nd) vaccination series. Protective immune response was detected among 84/91 children (92.3%). While 7/91 (7.7%) whose age were ≥10 years did not respond and had post-booster undetectable anti-HBs. About 80% of children with post-booster detectable anti-HBs showed significant protective immune response (anti-HBs ≥100 IU/L) and higher GMT (299.1 ± 3.6 IU/L) compared to those with undetectable 60% and 106.2 ± 12.9 IU/L respectively (P<0.05). No significant difference was detected as regards gender or residence, P>0.05. All children with history of rheumatic fever (7 children) or diabetes mellitus (1 child) developed immune response after 2(nd) vaccination series. A booster dose of HB vaccine may be unable to induce sufficient immunological response in children who had undetectable anti-HBs titers. Revaccination for non-responders is an important procedure to increase HBV protection rate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. A Comparison of Gene Expression Profiles between Glucocorticoid Responder and Non-Responder Bovine Trabecular Meshwork Cells Using RNA Sequencing

    PubMed Central

    Bermudez, Jaclyn Y.; Webber, Hannah C.; Brown, Bartley; Braun, Terry A.; Clark, Abbot F.; Mao, Weiming

    2017-01-01

    The most common ocular side effect of glucocorticoid (GC) therapy is GC-induced ocular hypertension (OHT) and GC-induced glaucoma (GIG). GC-induced OHT occurs in about 40% of the general population, while the other 60% are resistant. This study aims to determine the genes and pathways involved in differential GC responsiveness in the trabecular meshwork (TM). Using paired bovine eyes, one eye was perfusion-cultured with 100nM dexamethasone (DEX), while the fellow eye was used to establish a bovine TM (BTM) cell strain. Based on maximum IOP change in the perfused eye, the BTM cell strain was identified as a DEX-responder or non-responder strain. Three responder and three non-responder BTM cell strains were cultured, treated with 0.1% ethanol or 100nM DEX for 7 days. RNA and proteins were extracted for RNA sequencing (RNAseq), qPCR, and Western immunoblotting (WB), respectively. Data were analyzed using the human and bovine genome databases as well as Tophat2 software. Genes were grouped and compared using Student’s t-test. We found that DEX induced fibronectin expression in responder BTM cells but not in non-responder cells using WB. RNAseq showed between 93 and 606 differentially expressed genes in different expression groups between responder and non-responder BTM cells. The data generated by RNAseq were validated using qPCR. Pathway analyses showed 35 pathways associated with differentially expressed genes. These genes and pathways may play important roles in GC-induced OHT and will help us to better understand differential ocular responsiveness to GCs. PMID:28068412

  16. Low dose revaccination induces robust protective anti-HBs antibody response in the majority of healthy non-responder neonates.

    PubMed

    Jafarzadeh, A; Zarei, S; Shokri, F

    2008-01-10

    A sizeable proportion (1-10%) of healthy adults and to lesser extent neonates vaccinated with triple 10 microg hepatitis B (HB) vaccine fail to mount a protective antibody response. Revaccination with the same vaccine dose has proved to be effective in a significant number of primary non-responders. The influence of revaccination with lower vaccine doses however has not been studied adequately in non-responder neonates. This study was conducted to evaluate the influence of supplementary vaccination with a single low and standard dose of a recombinant hepatitis B (HB) vaccine in healthy Iranian non-responder neonates to primary vaccination. Iranian neonates unable to respond to primary vaccination with 10, 5 or 2.5 microg doses of recombinant HB vaccine were revaccinated with a single additional dose of the same concentration. Serum anti-HBs antibody titer was measured by sandwich ELISA. Administration of a single additional dose induced seroprotection (anti-HBs> or =10IU/L) in 10/12 (83%), 10/12 (83%) and 21/24 (87.5%) of non-responder neonates in 10, 5 and 2.5 microg vaccine recipients with geometric mean titers (and 95% confidence limits) of 1358 (258-7142), 401 (79-2038) and 164 (62-433) IU/L, respectively. The log-transformed antibody titer obtained for the 10 microg dose recipients was significantly higher than that of the 2.5 microg dose vaccinees (p=0.028). No significant differences in anti-HBs titer were observed between other groups of vaccinees. However, the total seroprotection rates obtained after administration of four low doses of 2.5 and 5 microg were significantly higher than that obtained after administration of the classical three 10 microg doses (p=0.029 and p=0.006, respectively). The total seroprotection rates were similar between all groups of vaccines receiving four doses of 2.5, 5 and 10 microg vaccine doses. These results indicate that a significant proportion of non-responder neonates can be induced to develop a protective anti

  17. Total Delay Is Associated with Unfavorable Treatment Outcome among Pulmonary Tuberculosis Patients in West Gojjam Zone, Northwest Ethiopia: A Prospective Cohort Study

    PubMed Central

    Gebreegziabher, Senedu Bekele; Bjune, Gunnar Aksel; Yimer, Solomon Abebe

    2016-01-01

    Background delay in diagnosis and treatment of tuberculosis (TB) may worsen the disease, increase mortality and enhance transmission in the community. This study aimed at assessing the association between total delay and unfavorable treatment outcome among newly diagnosed pulmonary TB (PTB) patients. Methods A prospective cohort study was conducted in West Gojjam Zone, Amhara Region of Ethiopia from October 2013 to May 2015. Newly diagnosed PTB patients who were ≥15 years of age were consecutively enrolled in the study from 30 randomly selected public health facilities. Total delay (the time period from onset of TB symptoms to first start of anti-TB treatment) was measured. Median total delay was calculated. Mixed effect logistics regression was used to analyze factors associated with unfavorable treatment outcome. Results Seven hundred six patients were enrolled in the study. The median total delay was 60 days. Patients with total delay of > 60 days were more likely to have unfavorable TB treatment outcome than patients with total delay of ≤ 60 days (adjusted odds ratio [AOR], 2.33; 95% confidence interval [CI], 1.04–5.26). Human immunodeficiency virus (HIV) positive TB patients were 8.46 times more likely to experience unfavorable treatment outcome than HIV negative TB patients (AOR, 8.46; 95% CI, 3.14–22.79). Conclusions Long total delay and TB/HIV coinfection were associated with unfavorable treatment outcome. Targeted interventions that can reduce delay in diagnosis and treatment of TB, and early comprehensive management of TB/HIV coinfection are needed to reduce increased risk of unfavorable treatment outcome. PMID:27442529

  18. [Phenotypic and genotypic diagnosis of bone and miliary tuberculosis in an HIV+ patient in Bogotá, Colombia].

    PubMed

    Jurado, Leonardo F; Murcia, Martha I; Hidalgo, Patricia; Leguizamón, John E; González, Lorena R

    2015-01-01

    Tuberculosis is the single most frequent cause of death by an infectious agent worldwide. Diagnosis of extra-pulmonary tuberculosis is not always possible through conventional methods, due to the long time required for cultures and the paucibacillary nature of samples; hence the need of rapid molecular methods. HIV infection increases the risk of tuberculosis, and HIV/tuberculosis coinfection is associated with higher mortality. We describe the case of a 56-year old mestizo male patient suspected of having tuberculosis who consulted the San Ignacio Hospital in Bogotá with a two-month history of a painful ulcerated lesion over the distal third area of the right forearm and in whom HIV coinfection was confirmed. Bone and pulmonary histological examination evidenced multiple granulomas, giant cells and fibrosis. Cultures and IS6110-PCR from lung and bone tissues were positive for Mycobacterium tuberculosis complex. Mycobacterium tuberculosis isolates were sensitive to first line drugs.

  19. Classification criteria for distinguishing cortisol responders from nonresponders to psychosocial stress: evaluation of salivary cortisol pulse detection in panel designs.

    PubMed

    Miller, Robert; Plessow, Franziska; Kirschbaum, Clemens; Stalder, Tobias

    2013-01-01

    Hypothalamic-pituitary-adrenal axis reactivity to acute stimulation is frequently assessed by repeated sampling of salivary cortisol. Researchers often strive to distinguish between individuals who show (responders) and those do not show (nonresponders) cortisol responses. For this, fixed threshold classification criteria, such as a 2.5-nmol/l baseline-to-peak increase, are frequently used. However, the performance of such criteria has not been systematically evaluated. Repeated salivary cortisol data from 504 participants exposed to either the Trier Social Stress Test (TSST; n = 309) or a placebo protocol (n = 195) were used for analyses. To obtain appropriate classifications of cortisol responders versus nonresponders, a physiologically plausible, autoregressive latent trajectory (ALT) mixture model was fitted to these data. Response classifications according to the ALT model and information on the experimental protocol (TSST versus placebo TSST) were then used to evaluate the performance of different proposed classifier proxies by receiver operating characteristics. Moment structure of cortisol time series was adequately accounted for by the proposed ALT model. The commonly used 2.5-nmol/l criterion was found to be overly conservative, resulting in a high rate of 16.5% false-negative classifications. Lowering this criterion to 1.5 nmol/l or using a percentage baseline-to-peak increase of 15.5% as a threshold yielded improved performance (39.3% and 26.7% less misclassifications, respectively). Alternative classification proxies (1.5 nmol/l or 15.5% increase) are able to effectively distinguish between cortisol responders and nonresponders and should be used in future research, whenever statistical response class allocation is not feasible.

  20. Nonresponders, partial responders, and complete responders to PDE5 inhibitors therapy according to IIEF criteria: validation of an anchor-based treatment responder classification.

    PubMed

    Yang, May; Ni, Xiao; Sontag, Angelina; Litman, Heather J; Rosen, Raymond C

    2013-12-01

    Despite widespread use of the International Index of Erectile Function (IIEF) in erectile dysfunction (ED) research, there are no published criteria for classifying ED treatment responders in clinical trials or patient management settings. A new classification for treatment response in men with ED has been developed and validated in a large clinical trial database. The study aims to test discriminant and convergent validity of the responder classification and examine the role of covariates. Treatment assignment was used to test discriminant validity. The diary-based Sexual Encounter Profile (SEP) question ("Did your erection last long enough for you to have successful intercourse?") and Global Assessment Question (GAQ) ("Has the treatment you have been taking over the past study interval improved your erections?") were used to evaluate convergent validity. Chi-square and Cochran-Armitage trend tests were used to examine outcome associations. Logistic regression was used to further assess the relationship of outcomes controlling for covariates. The classification measure was developed and validated in a database from 17 clinical trials in 3,252 men with ED randomized to placebo or tadalafil. The treatment responder is defined as complete (erectile function [EF] ≥ 26); partial (EF < 26; met minimal clinically important difference [MCID] criteria); or nonresponder following treatment (EF < 26; did not meet MCID). The new responder definition performed consistently well in all prespecified tests of validity. Eighty-nine percent of subjects classified as complete responders were in the treatment group, and the responder definition was associated with changes on the SEP and GAQ measures, respectively (SEP odds ratio [OR] = 14, 95% confidence intervals [CI] 11-17; GAQ OR = 50, 95% CI 39-88; complete vs. nonresponders). We developed and validated a novel method of defining an ED treatment responder based on multiple IIEF criteria and using other measures (SEP, GAQ) for

  1. Characteristics of clinical measurements between biomechanical responders and non-responders to a shoe designed for knee osteoarthritis.

    PubMed

    Kim, Yongwook; Richards, Jim; Lidtke, Roy H; Trede, Renato

    2017-09-29

    The purpose of this study was to investigate the characteristics of biomechanical and clinical measurements in relation to the knee adduction moment when wearing a standard shoe and a shoe design for individuals with knee osteoarthritis (Flex-OA). Kinematic and kinetic data were collected from thirty-two healthy individuals (64 knees) using a ten camera motion analysis system and four force plates. Subjects performed 5 walking trials under the two conditions and the magnitude of individuals' biomechanical responses where explored in relation to the clinical assessment of the Foot Posture Index, hip rotation range, strength of hip rotators, and active ankle-foot motion, all of which have been described as possible compensation mechanisms in knee osteoarthritis. Significant reductions in the first peak of the knee adduction moment (KAM) during stance phase (9.3%) were recorded (p<0.0001). However, despite this difference, 22 of 64 knees showed either no change or an increased KAM, indicating a non-response or negative-response to the Flex-OA shoe. Significant differences were observed between the responder and non-responder subgroups in the hip rotation range ratio (p=0.044) and the hip rotators strength ratio (p=0.028). Significant differences were seen in clinical assessments of hip rotation range and hip rotator strength between responders and non-responders using a cut-off of 0.02Nm/kg change in the KAM. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Parents' difficulties as co-therapists in CBT among non-responding youths with anxiety disorders: Parent and therapist experiences.

    PubMed

    Lundkvist-Houndoumadi, Irene; Thastum, Mikael; Nielsen, Klaus

    2016-07-01

    No increased effect has been associated with parent involvement in cognitive behavioral therapy (CBT) for youths with anxiety disorders. The purpose of this study was to explore parent and therapist experiences of CBT among non-responding youths with anxiety disorders, with a primary focus on parent involvement in therapy. Interpretative phenomenological analysis was applied to 24 sets of semi-structured interviews with families and therapists of anxiety-disordered youths who had not profited from CBT with parental inclusion. From the superordinate theme parents' difficulties acting as co-therapists, which emerged from the analyses, two master themes represented the perspectives of parents (difficulty working together with the youth and feeling unqualified, with limited resources), and two represented the perspectives of therapists (family dynamics stood in the way of progress and difficulty transferring control to parents). Parent and therapist experiences complemented each other, offering two different perspectives on parent difficulties as co-therapists. However, the two groups' views on their respective roles in therapy were in conflict. Parents wished to remain being "just the parents" and for the experts to take over, while therapists wished to act as facilitators transferring the control to parents. Clinical implications are drawn for parental involvement and enhancement of treatment outcomes for likely non-responders. © The Author(s) 2015.

  3. Non-responders to egg grown influenza vaccine seroconvert after booster immunization with MDCK cell grown vaccine.

    PubMed

    Oxford, John S; Al-Jabri, Ali A; Lambkin, Robert; Palache, A M; Fleming, D M

    2003-06-20

    We have investigated whether 'at risk' subjects who did not respond serologically during a pre-study vaccination with a commercial egg grown influenza sub-unit vaccine would respond to a subsequent vaccination with either a single dose of MDCK cell grown influenza vaccine or a standard egg grown influenza vaccine containing the same virus strains. We studied 48 non-responder subjects with a mean age 67.5, range: 34-82 years. In this non-responder group the increased immune response that was detected after boosting with an MDCK cell derived vaccine response was variable and relatively modest, except for the A/Texas strain in the vaccine. The proportion of subjects, with an HI titre of >/=40 (protective antibody titre) increased from 50 to 83% (A/Texas strain), from 13 to 25% (B/Harbin strain) and from 38 to 46% (A/Wuhan strain). In comparison a booster vaccination with egg-derived influenza vaccine resulted in an increase immune response with an HI antibody titre >/=40 for two of the three strains, namely from 17 to 58% for the B/Harbin strain and from 8 to 33% for the A/Wuhan strain.

  4. Effect on trend estimates of the difference between survey respondents and non-respondents: results from 27 populations in the WHO MONICA Project.

    PubMed

    Tolonen, Hanna; Dobson, Annette; Kulathinal, Sangita

    2005-01-01

    In the World Health Organization (WHO) MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease) Project considerable effort was made to obtain basic data on non-respondents to community based surveys of cardiovascular risk factors. The first purpose of this paper is to examine differences in socio-economic and health profiles among respondents and non-respondents. The second purpose is to investigate the effect of non-response on estimates of trends. Socio-economic and health profile between respondents and non-respondents in the WHO MONICA Project final survey were compared. The potential effect of non-response on the trend estimates between the initial survey and final survey approximately ten years later was investigated using both MONICA data and hypothetical data. In most of the populations, non-respondents were more likely to be single, less well educated, and had poorer lifestyles and health profiles than respondents. As an example of the consequences, temporal trends in prevalence of daily smokers are shown to be overestimated in most populations if they were based only on data from respondents. The socio-economic and health profiles of respondents and non-respondents differed fairly consistently across 27 populations. Hence, the estimators of population trends based on respondent data are likely to be biased. Declining response rates therefore pose a threat to the accuracy of estimates of risk factor trends in many countries.

  5. Upregulation of IL-21 Receptor on B Cells and IL-21 Secretion Distinguishes Novel 2009 H1N1 Vaccine Responders from Nonresponders among HIV-Infected Persons on Combination Antiretroviral Therapy

    PubMed Central

    Pallikkuth, Suresh; Kanthikeel, Sudheesh Pilakka; Silva, Sandra Y.; Fischl, Margaret; Pahwa, Rajendra; Pahwa, Savita

    2011-01-01

    Mechanisms underlying failure of novel 2009 H1N1 influenza vaccine-induced Ab responses in HIV-infected persons are poorly understood. This study prospectively evaluated 16 HIV-infected patients on combination antiretroviral therapy and eight healthy controls (HC) who received a single 15 μg dose of nonadjuvanted novel 2009 H1N1 influenza vaccine during the 2009 H1N1 epidemic. Peripheral blood was collected at baseline (T0) and at 7 d (T1) and 28 d (T2) postvaccination for evaluation of immune responses. Prevaccination hemagglutination inhibition Ab titer was <1:20 in all except one study participant. At T2, all HC and 8 out of 16 patients (50%) developed a vaccine-induced Ab titer of ≥1:40. Vaccine responder (R) and vaccine nonresponder patients were comparable at T0 in age, CD4 counts, virus load, and B cell immunophenotypic characteristics. At T2, HC and R patients developed an expansion of phenotypic and functional memory B cells and ex vivo H1N1-stimulated IgG Ab-secreting cells in an ELISPOT assay. The memory B cell response was preceded by a significant expansion of plasmablasts and spontaneous H1N1-specific Ab-secreting cells at T1. At T2, HC and R patients also exhibited significant increases in serum IL-21 levels and in the frequency and mean fluorescence intensity of IL-21R–expressing B cells, which correlated with serum H1N1 Ab titers. Vaccine nonresponder patients failed to develop the above-described vaccine-induced immunologic responses. The novel association of novel 2009 H1N1 vaccine-induced Ab responses with IL-21/IL-21R upregulation and with development of memory B cells and plasmablasts has implications for future research in vaccine design. PMID:21531891

  6. Penile Low Intensity Shock Wave Treatment is Able to Shift PDE5i Nonresponders to Responders: A Double-Blind, Sham Controlled Study.

    PubMed

    Kitrey, Noam D; Gruenwald, Ilan; Appel, Boaz; Shechter, Arik; Massarwa, Omar; Vardi, Yoram

    2016-05-01

    We performed sham controlled evaluation of penile low intensity shock wave treatment effect in patients unable to achieve sexual intercourse using PDE5i (phosphodiesterase type 5 inhibitor). This prospective, randomized, double-blind, sham controlled study was done in patients with vasculogenic erectile dysfunction who stopped using PDE5i due to no efficacy. All patients had an erection hardness score of 2 or less with PDE5i. A total of 58 patients were randomized, including 37 treated with low intensity shock waves (12 sessions of 1,500 pulses of 0.09 mJ/mm(2) at 120 shock waves per minute) and 18 treated with a sham probe. In the sham group 16 patients underwent low intensity shock wave treatment 1 month after sham treatment. All patients were evaluated at baseline and 1 month after the end of treatment using validated erectile dysfunction questionnaires and the flow mediated dilatation technique for penile endothelial function. Erectile function was evaluated while patients were receiving PDE5i. In the low intensity shock wave treatment group and the sham group 54.1% and 0% of patients, respectively, achieved erection hard enough for vaginal penetration, that is an EHS (Erection Hardness Score) of 3 (p <0.0001). According to changes in the IIEF-EF (International Index of Erectile Function-Erectile Function) score treatment was effective in 40.5% of men who received low intensity shock wave treatment but in none in the sham group (p = 0.001). Of patients treated with shock waves after sham treatment 56.3% achieved erection hard enough for penetration (p <0.005). Low intensity shock wave treatment is effective even in patients with severe erectile dysfunction who are PDE5i nonresponders. After treatment about half of them were able to achieve erection hard enough for penetration with PDE5i. Longer followup is needed to establish the place of low intensity shock wave treatment in these challenging cases. Copyright © 2016 American Urological Association Education

  7. Results and their implications from comparing respondents and proxy responses for non-respondents with cognitive difficulties on a telephone survey.

    PubMed

    Adams, Mary

    2017-01-01

    Limited study has been done on proxy responses for non-respondents with subjective cognitive decline (SCD) on the Behavioral Risk Factor Surveillance System (BRFSS). To directly compare results for survey respondents with SCD with those for proxies provided for non-respondents with SCD. Publicly available 2011 BRFSS data from 120,485 households in 21 states were analyzed using Stata. Respondents ages 40 and older with SCD (n = 10,831) were compared with proxy responses for non-respondents ages 40 and older with SCD (n = 4296) living in households where the respondent did not have SCD. Outcome measures included functional difficulties associated with their SCD, needing help, receiving informal care, talking with a healthcare provider about their SCD, getting treatment, and having a dementia diagnosis. Logistic regression for each outcome controlled for age, household income, state of residence, and number of household adults. Non-respondents were significantly more likely than respondents by Pearson chi square tests with alpha = 0.05 to report all 6 outcomes. Adjusted odds ratios comparing non-respondents with respondents ranged from 2.61 (95% confidence interval: 2.22-3.07) for needing help, to 8.99 (6.60-12.24) for a dementia diagnosis and confirmed unadjusted results. Respondent results only represent adults capable of answering a telephone survey. To represent all household adults and avoid nonresponse bias that may under-represent the true population parameters by as much as 70%, results must include both respondents and non-respondents. Other measures may be similarly affected if they inhibit one's ability to respond to a telephone survey (e.g. disability, stroke). Copyright © 2016 Elsevier Inc. All rights reserved.

  8. A prospective trial of bupropion SR augmentation of partial and non-responders to serotonergic antidepressants.

    PubMed

    DeBattista, Charles; Solvason, H Brent; Poirier, Jennifer; Kendrick, Ellen; Schatzberg, Alan F

    2003-02-01

    Many patients fail to achieve an adequate response to a given antidepressant trial. The best-studied augmentation agents, lithium and thyroid supplementation are less commonly used. Augmenting antidepressants with bupropion has become an increasingly common strategy in the treatment of resistant depression. Several case reports and 2 open label studies suggest efficacy of this strategy. The purpose of this study is to further examine the utility of bupropion sustained release (SR) augmentation in patients with inadequate response to selective serotonin reuptake inhibitors. Patients who met DSM-IV criteria for major depression and had failed to achieve adequate response to an SSRI were considered for this study. Eligible patients were required to have a score of 16 on the 24-item Hamilton Depression Rating Scale (HDRS). Patients were treated openly for 6 weeks with bupropion SR added to their existing antidepressant. The dose range of bupropion was 150 to 300 mg per day. At each visit, patients were assessed using the Beck Depression Inventory (BDI), the Hamilton Depression Ratings Scale (HDRS), and the Clinical Global Impression (CGI). Twenty-eight patients (12 men, 16 women) entered the study. Twenty-five patients completed the six-week trial. With respect to the clinical benefit of bupropion SR augmentation, 15 out of 28, or 54% of patients, were classified as responders, showing a decrease in their HDRS or BDI scores of 50% or more between baseline and Week 6. This prospective, open-label trial supports the use of bupropion SR in the augmentation of SSRIs and venlafaxine. Placebo controlled trials should be completed to further evaluate the efficacy of this strategy.

  9. [Horizons and perspectives on the problem of non--responders to cardiac resynchronization therapy.

    PubMed

    Carità, Patrizia; Corrado, Egle; Pontone, Gianluca; Curnis, Antonio; Nogara, Angela; Mignano, Antonino; Verdecchia, Massimo; Ciaramitaro, Gianfranco; Novo, Salvatore; Coppola, Giuseppe

    2017-01-01

    Cardiac resynchronization therapy (CRT) has been shown as a successful strategy in the treatment of patients with heart failure and electrical dyssincrony. However, a significant proportion of implanted patients fails to respond sufficiently or in a predictable manner. Consequently, non response to CRT remains a valuable problem in clinical practice. In order to improve CRT response and long-term clinical benefits, the proper evaluation of patient's global frialty, the technology improvement, the multimodality imaging approach and the use of simple and low cost electrographic parameters (to verify effective biventricular capture and QRS narrowing) could play a important role. Therefore, the integration of various medical expertises (clinical cardiology, cardiac advanced imaging, electrophysiology) is a crucial element in order to achive the maximal benefits from this promising tecnique. In the multistep process (from patients evaluation to results verification) the follow-up even from the earliest post implantation phase, should be managed with great attention having the potential for impact the prognosis. This brief review focus the problem of non responder to CRT, giving particular attention to the different variables that may play a role (comorbilities, improvement in the tecnology of device implantation, role of multimodality imaging and electrocardiographic parameters).

  10. D-Cycloserine for Treatment Nonresponders with Obsessive-Compulsive Disorder: A Case Report

    ERIC Educational Resources Information Center

    Norberg, Melissa M.; Gilliam, Christina M.; Villavicencio, Anna; Pearlson, Godfrey D.; Tolin, David F.

    2012-01-01

    Despite being the most effective treatment available, as many as one third of patients who receive exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD) do not initially respond to treatment. Recent research suggests that the n-methyl d-aspartate (NMDA) receptor partial agonist D-Cycloserine (DCS) may speed up the course…

  11. D-Cycloserine for Treatment Nonresponders with Obsessive-Compulsive Disorder: A Case Report

    ERIC Educational Resources Information Center

    Norberg, Melissa M.; Gilliam, Christina M.; Villavicencio, Anna; Pearlson, Godfrey D.; Tolin, David F.

    2012-01-01

    Despite being the most effective treatment available, as many as one third of patients who receive exposure and response prevention (ERP) for obsessive-compulsive disorder (OCD) do not initially respond to treatment. Recent research suggests that the n-methyl d-aspartate (NMDA) receptor partial agonist D-Cycloserine (DCS) may speed up the course…

  12. Treatment of primary biliary cholangitis ursodeoxycholic acid non-responders: A systematic review.

    PubMed

    Suraweera, Duminda; Rahal, Harman; Jimenez, Melissa; Viramontes, Matthew; Choi, Gina; Saab, Sammy

    2017-05-18

    Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic cholestatic liver disease characterized by an immune mediated destruction of intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) has been the primary medication for the treatment of PBC, resulting in improved liver tests, resolution of symptoms and increased transplant free survival. However, not all patients respond to UDCA. The aim of this systematic review is to provide an evidence based assessment of the medications that have been studied in patients who are refractory to UDCA. We performed a systematic literature search on MEDLINE and the Cochrane Database of Systematic Reviews of the published literature. A total of 23 articles fulfilling our inclusion criteria were found. Several studies have shown an improvement in liver biochemistries with the use of obeticholic acid in conjunction with UDCA. Fibrates, including fenofibrate and bezafibrate, have evidence supporting benefit in this population but need more robust studies to confirm these observational results. Neither obeticholic acid nor fibrates have shown to increase transplant free survival. While there may be some benefit with methotrexate, colchicine, budesonide, mycophenolate mofetil and azathioprine, these findings were not consistent and the benefits were marginal. Further investigation is needed. In patients with PBC refractory to UDCA, obeticholic acid or a fibrate is a reasonable choice as an adjunctive treatment to UDCA. Further investigation with randomized controlled trials is needed to provide high quality evidence to formulate standardized therapies in this difficult to treat population. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. An Open Trial of Intensive Family Based Cognitive-Behavioral Therapy in Youth with Obsessive-Compulsive Disorder Who Are Medication Partial Responders or Nonresponders

    ERIC Educational Resources Information Center

    Storch, Eric A.; Lehmkuhl, Heather D.; Ricketts, Emily; Geffken, Gary R.; Marien, Wendi; Murphy, Tanya K.

    2010-01-01

    This study reports an open-trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD). Thirty primarily Caucasian youth with OCD (range = 7-19 years; 15 girls) who were partial responders or nonresponders to two or more medication trials that were delivered either serially or…

  14. Visual Motor Integration as a Screener for Responders and Non-Responders in Preschool and Early School Years: Implications for Inclusive Assessment in Oman

    ERIC Educational Resources Information Center

    Emam, Mahmoud Mohamed; Kazem, Ali Mahdi

    2016-01-01

    Visual motor integration (VMI) is the ability of the eyes and hands to work together in smooth, efficient patterns. In Oman, there are few effective methods to assess VMI skills in children in inclusive settings. The current study investigated the performance of preschool and early school years responders and non-responders on a VMI test. The full…

  15. An Open Trial of Intensive Family Based Cognitive-Behavioral Therapy in Youth with Obsessive-Compulsive Disorder Who Are Medication Partial Responders or Nonresponders

    ERIC Educational Resources Information Center

    Storch, Eric A.; Lehmkuhl, Heather D.; Ricketts, Emily; Geffken, Gary R.; Marien, Wendi; Murphy, Tanya K.

    2010-01-01

    This study reports an open-trial of family-based cognitive-behavioral therapy (CBT) in children and adolescents with obsessive-compulsive disorder (OCD). Thirty primarily Caucasian youth with OCD (range = 7-19 years; 15 girls) who were partial responders or nonresponders to two or more medication trials that were delivered either serially or…

  16. Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine.

    PubMed

    Cardell, Kristina; Akerlind, Britt; Sällberg, Matti; Frydén, Aril

    2008-08-01

    Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs) and are considered to be nonresponders. A total of 48 nonresponders and 20 subjects naive to the HBV vaccine received a double dose of combined hepatitis A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and 1 month after each dose. Among 44 nonresponders, protective anti-HBs levels were found in 26 (59%) after the first dose and in 42 (95%) after the third dose. Among the control subjects, the corresponding figures were 10% and 100%, respectively. All subjects seroconverted to anti-HAV. The titers of both anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P< .01). Revaccination of nonresponders to the standard hepatitis B vaccine regimen with a double dose of the combined hepatitis A and B vaccine was highly effective. This is most likely explained by the increased dose, a positive bystander effect conferred by the hepatitis A vaccine, or both.

  17. Visual Motor Integration as a Screener for Responders and Non-Responders in Preschool and Early School Years: Implications for Inclusive Assessment in Oman

    ERIC Educational Resources Information Center

    Emam, Mahmoud Mohamed; Kazem, Ali Mahdi

    2016-01-01

    Visual motor integration (VMI) is the ability of the eyes and hands to work together in smooth, efficient patterns. In Oman, there are few effective methods to assess VMI skills in children in inclusive settings. The current study investigated the performance of preschool and early school years responders and non-responders on a VMI test. The full…

  18. A one-year open-label trial of risperidone augmentation in lithium nonresponder youth with preschool-onset bipolar disorder.

    PubMed

    Pavuluri, Mani N; Henry, David B; Carbray, Julie A; Sampson, Gwen A; Naylor, Michael W; Janicak, Philip G

    2006-06-01

    The aim of this study was to assess the safety and efficacy of risperidone augmentation of lithium in preschool-onset bipolar disorder (BD) among youth who insufficiently respond to lithium monotherapy. Thirty-eight subjects between the ages of 4 and 17 years (mean age = 11.37 +/- 3.8 years) with onset of BD in preschool years (manic or mixed episode) entered this 12-month trial. All subjects received lithium monotherapy. Patients who failed to adequately respond to lithium monotherapy after 8 weeks and those who relapsed after an initial response were given risperidone augmentation for up to 11 months. The Young Mania Rating Scale (YMRS) was the primary outcome measure. Response was defined as a > or =50% decrease from baseline. Additional data were collected on diagnostic comorbidity, family history, number of hospitalizations, perinatal risk factors, history of physical or sexual abuse, Child Depression Rating Scale-Revised (CDRS-R), Clinical Global Impression (CGI) scale for BD (CGI-BP), Children's Global Assessment Scale (C-GAS), and adverse medication effects. Of the 38 subjects treated with lithium monotherapy, 17 responded, whereas 21 required augmentation with risperidone. Response rate in the youths treated with lithium + risperidone was 85.7% (n = 18/21). Significant predictors of inadequate response to lithium monotherapy requiring augmentation were: (1) attention-deficit/hyperactivity disorder (ADHD), (2) severity at baseline, (3) history of sexual or physical abuse, and (4) preschool age. Combination treatment of lithium and risperidone was found to be safe and well tolerated. A substantial proportion of youth with a history of preschool-onset BD treated with lithium were either nonresponders or partial responders. Subsequent augmentation of lithium with risperidone in these cases was well tolerated and efficacious. Potential predictors of lithium nonresponse identified in this study may guide the choice of medications earlier in the treatment process.

  19. Successful treatment of a cardiac resynchronization therapy nonresponder by identifying lead malpositioning

    PubMed Central

    Prasad, Karthik Venkatesh; Ferreira, Scott Wayne; Mehdirad, Ali Akbar

    2017-01-01

    This case describes some of the commonly overlooked device-related issues in patients who have reportedly failed to respond to cardiac resynchronization therapy (CRT). The case demonstrates voltage-dependent right ventricular capture instead of right atrial capture by a subtly malpositioned right atrial lead. CRT therapy failed to improve symptoms of heart failure and the diagnosis of “CRT nonresponder” was made. With a detailed fact-finding approach, the mechanism behind this nonresponse was identified, and the outcome of CRT was significantly improved with rectification of the problems. PMID:28405094

  20. Successful use of the excimer laser for generalized psoriasis in an ustekinumab non-responder.

    PubMed

    Malakouti, Mona; Brown, Gabrielle Elena; Sorenson, Eric; Leon, Argentina; Koo, John; Levin, Ethan Charles

    2014-12-16

    Effective treatments for moderate to severe psoriasis are phototherapy and biologics. These treatments are similar in that they both decrease cutaneous immune system hyperactivity yet do so via different mechanisms. Our patient, a 63 year old Asian male had a rapid response to treatment with the high dose excimer laser, having previously failed treatment with 28 weeks of ustekinumab therapy. A pre-treatment biopsy of a psoriatic plaque was found to contain relatively low levels of IFN-γ (Th1) and IL-17 (Th17) secreting T cells. Following treatment with the excimer laser, the patient had a quick improvement in PASI that was reflected by a 3-fold reduction in the number of live T cells found in the post-treatment biopsy. Although ustekinumab and the excimer laser both result in decreased levels of these cytokines, the excimer laser directly causes apoptosis of T cells and induces DNA damage in antigen presenting cells. Thus, the broader effects of phototherapy on immune cells compared to the targeted inhibition of IL-12 and IL-23 by ustekinumab likely account for the superior response observed.

  1. Augmentative quetiapine in partial/nonresponders with generalized anxiety disorder: a randomized, placebo-controlled study.

    PubMed

    Altamura, Alfredo Carlo; Serati, Marta; Buoli, Massimiliano; Dell'Osso, Bernardo

    2011-07-01

    Generalized anxiety disorder (GAD) is a chronic and disabling condition. The aim of this study was to evaluate the effectiveness of low-dose augmentative quetiapine (mean dose=50 mg/day) in patients with GAD and partial/no response to selective serotonin reuptake inhibitors (SSRIs). Twenty patients with GAD and partial/no response to SSRIs were randomized to quetiapine (n=10) or placebo (n=10) for 8 weeks, continuing their treatment with SSRIs. Analyses of variance with repeated measures on Hamilton Anxiety Rating Scale (HAM-A) and Clinical Global Impression (CGIs; severity of illness) were carried out at baseline and after 8 weeks and the number of responders/remitters was computed and compared between the groups. HAM-A scores at baseline were 15.60 (± 4.48) in the placebo group and 18.50 (± 6.59) in the quetiapine group, and at the end-point, HAM-A scores in the placebo group were 10.40 (± 4.88) and 9.20 (± 5.86) in the quetiapine group. A significant time-by-treatment effect was found on the HAM-A (F=5.19, P=0.035) and CGIs scores (F=19.60, P<0.001) in favor of the quetiapine group. The number of responders was numerically superior in the quetiapine group (60 vs. 30%) without reaching statistical significance (χ=1.82, degree of freedom=1, P=0.37, φ=0.30). Remitters were 40% for the quetiapine group versus 20% for the placebo group (χ=0.95, degree of freedom=1, P=0.63, φ=0.22). Low-dose augmentative quetiapine may be an useful treatment option for patients with GAD and partial/no response to SSRIs. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results. Larger randomized controlled trials are warranted to confirm these data.

  2. Sexual functioning and satisfaction in nonresponders to testosterone gel: Potential effectiveness of retreatment in hypogonadal males.

    PubMed

    Steidle, Christopher; Witt, Michael A; Matrisciano, Justin; Block, Jon E

    2005-01-01

    There is a slow but continuous decline in testosterone (T) levels with age, with a substantial percentage of males exhibiting T levels in the hypogonadal range. This age-dependent decline in circulating androgens is associated, in large part, with reduced sexual functioning and libido. The effectiveness of TestimR 1% (Auxilium Pharmaceuticals, Inc., Norristown, Pennsylvania) topical T gel was evaluated in older hypogonadal males who failed to experience satisfactory symptom relief after treatment with AndroGelR 1% (Solvay Pharmaceuticals, Inc., Marietta, Georgia). In this open-label study, consecutive subjects were assigned randomly to experimental treatment with Testim 1% (5 g) or to maintenance therapy (control group) with AndroGel 1% (5 g). Seventy-six experimental subjects and 75 control subjects were followed for 4 weeks to evaluate improvements in sexual functioning and satisfaction. Changes from baseline in the 5 domains of the Brief Male Sexual Function Inventory were compared between groups. The mean percentage improvement favored the experimental treatment in sexual drive (23% vs 16%, P < 0.3), erectile function (32% vs 8%, P < 0.03), ejaculatory function (11% vs 9%, P < 0.4), problem assessment (47% vs 12%, P < 0.01), and sexual satisfaction (62% vs 23%, P < 0.02). A greater percentage of subjects also reported satisfaction with the experimental treatment (55% vs 33%, P < 0.02), and these subjects were less likely to require upward dose titration at the final follow-up visit (53% vs 72%, P < 0.03). Consideration of Testim 1% gel in patients who have an inadequate response to prior T therapy is encouraged, although it is difficult to estimate the contribution of nonspecific study effects (eg, placebo) in this trial.

  3. Influence of HIV infection on response to tenofovir in patients with chronic hepatitis B.

    PubMed

    Plaza, Zulema; Aguilera, Antonio; Mena, Alvaro; Vispo, Eugenia; Sierra-Enguita, Rocío; Tomé, Santiago; Pedreira, José; Rodriguez, Carmen; Barreiro, Pablo; del Romero, Jorge; Soriano, Vicente; Poveda, Eva

    2013-09-10

    HIV worsens the natural history of chronic hepatitis B virus (HBV) infection. Suppression of HBV replication slows progression of liver damage. Information about the influence of HIV on response to tenofovir in HIV/HBV-coinfected patients is scarce. All individuals with persistent HBsAg+ at four clinics in Spain were identified. Information from the subset that initiated tenofovir therapy was examined. A total of 176 patients with chronic hepatitis B were evaluated, of whom 138 (78.4%) were coinfected with HIV. Prior lamivudine exposure was extensive in both groups, and nearly half of HBV viremic patients harboured drug resistance mutations. Most patients took tenofovir coformulated along with emtricitabine (Truvada). Of 101 HBV viremic patients at the time of beginning tenofovir (78 with HIV coinfection and 33 with HBV alone), a similar proportion achieved undetectable HBV-DNA at weeks 24, 48 and 96 of tenofovir therapy. Interestingly, HIV/HBV-coinfected patients with positive HBeAg showed a lower response than HBeAg-negatives. In multivariate analysis, however, baseline serum HBV-DNA was the only predictor of virological response to tenofovir. The antiviral efficacy of tenofovir is similar in HIV/HBV-coinfected and HBV-monoinfected patients, achieving undetectable HBV-DNA nearly 90% of patients at week 96 of therapy. Baseline serum HBV-DNA is the major determinant of time-trends in virological response, with no significant influence of HBeAg, drug resistance mutations nor coinfection with hepatitis C or delta viruses.

  4. Low cross-neutralization of hepatitis C correlates with liver disease in immunocompromized patients.

    PubMed

    Maurin, Guillemette; Halgand, Boris; Bruscella, Patrice; Fresquet, Judith; Duclos-Vallée, Jean-Charles; Roque-Afonso, Anne-Marie; Cosset, François-Loïc; Samuel, Didier; Lavillette, Dimitri; Féray, Cyrille

    2015-06-01

    Chronic hepatitis C virus (HCV) infection causes severe liver disease in HIV-infected patients and liver transplant recipients. The impact of serum and immunoglobulin on viral entry was analysed in these patients. Sera from 60 anti-HCV positive patients, including 30 who were also anti-HIV positive, were tested with HCVpp from different genotypes (1a, 1b, 3 and 4) and with HCVcc (H77/JFH1). Seventeen HIV-seropositive and 13 HIV-seronegative patients with decompensated liver disease were studied before and after liver transplant. Serum neutralization was markedly lower after liver transplant and in HIV patients than in mono-infected immune-competent individuals. This effect was due to low antibody-mediated neutralization. In HIV patients, low neutralization was correlated with low lymphocyte T CD4 cell counts and the severity of liver disease. To characterize neutralization, we tested HCVpp lacking hypervariable region (HVR1) and SR-BI receptor cholesterol transfer inhibition by BLT-4. These experiments showed that neutralization was strongly dependent on the HVR1 and the SR-BI receptor. HVR1 sequences showed that selective pressures were low in immune-compromised patients and highly correlated to HCV neutralization after liver transplant. Neutralization experiments were reproduced with HCV strain JFH1. Serum neutralization in HIV-coinfected patients and HCV-infected liver transplant recipients is poor enhancing HCV entry through HVR1/SR-BI interplay. This may contribute to the severity of hepatitis C in these settings.

  5. Successful Tuberculosis Treatment Outcomes among HIV/TB Coinfected Patients Down-Referred from a District Hospital to Primary Health Clinics in Rural South Africa

    PubMed Central

    Jacobson, Karen B.; Moll, Anthony P.; Friedland, Gerald H.; Shenoi, Sheela V.

    2015-01-01

    Background HIV and tuberculosis (TB) coinfection remains a major public health threat in sub-Saharan Africa. Integration and decentralization of HIV and TB treatment services are being implemented, but data on outcomes of this strategy are lacking in rural, resource-limited settings. We evaluated TB treatment outcomes in TB/HIV coinfected patients in an integrated and decentralized system in rural KwaZulu-Natal, South Africa. Methods We retrospectively studied a cohort of HIV/TB coinfected patients initiating treatment for drug-susceptible TB at a district hospital HIV clinic from January 2012-June 2013. Patients were eligible for down-referral to primary health clinics(PHCs) for TB treatment completion if they met specific clinical criteria. Records were reviewed for patients’ demographic, baseline clinical and laboratory information, past HIV and TB history, and TB treatment outcomes. Results Of 657(88.7%) patients, 322(49.0%) were female, 558(84.9%) were new TB cases, and 572(87.1%) had pulmonary TB. After TB treatment initiation, 280(42.6%) were down-referred from the district level HIV clinic to PHCs for treatment completion; 377(57.4%) remained at the district hospital. Retained patients possessed characteristics indicative of more severe disease. In total, 540(82.2%) patients experienced treatment success, 69(10.5%) died, and 46(7.0%) defaulted. Down-referred patients experienced higher treatment success, and lower mortality, but were more likely to default, primarily at the time of transfer to PHC. Conclusion Decentralization of TB treatment to the primary care level is feasible in rural South Africa. Treatment outcomes are favorable when patients are carefully chosen for down-referral. Higher mortality in retained patients reflects increased baseline disease severity while higher default among down-referred patients reflects failed linkage of care. Better linkage mechanisms are needed including improved identification of potential defaulters, increased

  6. Prevalence and genotypic variability of TTV in HIV-infected patients.

    PubMed

    Sherman, K E; Rouster, S D; Feinberg, J

    2001-11-01

    TT virus is a small, circular DNA virus, that has been associated with transfusion hepatitis. We sought to determine the prevalence of TT virus (TTV) in patients with human immunodeficiency virus (HIV) infection and to characterize the virus in terms of genotypic variability and in the relationship to CD4+, HIV viral loads, HCV/HIV coinfection, and ALT abnormalities. A cross-sectional analysis of HIV-infected patients in the United States, including 86 HIV-positive subjects and 118 HIV-negative controls was performed. TTV was detected using a seminested PCR technique. Samples underwent cloning and sequence analysis and/or RFLP to determine genotype. Thirty-eight percent of HIV-positive patients had TTV infection versus 14.4% of patients within the matching cohort (P = 0.0009). The highest rate of TTV infection was in patients with concurrent HCV/HIV infection (54% vs 30%, P = 0.038). HIV-infected subjects with TTV had lower ALT levels than those without TTV (P = 0.036). Intravenous drug use was the leading factor associated with TTV positivity among HIV-positive subjects. Mixed genotypes were more common in those with HIV. Therefore, TTV prevalence, ALT levels, and genomic heterogeneity of TTV all seem to be altered in patients with HIV.

  7. Treatment of acute hepatitis C virus infection in HIV+ patients: Dutch recommendations for management.

    PubMed

    Arends, J E; Lambers, F A E; van der Meer, J T M; Schreij, G; Richter, C; Brinkman, K; Hoepelman, A I M

    2011-01-01

    With a rising incidence of acute hepatitis C virus (HCV) infection in patients coinfected with the human immunodeficiency virus (HIV), there is a need for evidence-based treatment recommendations. There are no randomised trials available and published studies differ with respect to design, patient characteristics and number of patients included, making a comparison between studies difficult. However, it is critical to standardise treatment for this group of patients in order to optimise the outcome of therapy. The Dutch Society for HIV Physicians proposed to write recommendations for the treatment of acute HCV in HIV -coinfected patients. Combination therapy with pegylated interferon-alpha and ribavirin is the preferred regimen initiated preferably within 12 weeks after the diagnosis of acute HCV. A treatment duration of 24 weeks is recommended in case of a favourable virological response (either achievement of a rapid virological response or a > 2 log10 decrease plus undetectable HCV-RNA at week 12). In all other patients prolonging the duration of therapy to 48 weeks should be considered.

  8. Factors Associated with Mortality among Patients on TB Treatment in the Southern Region of Zimbabwe, 2013

    PubMed Central

    Sandy, Charles; Masuka, Nyasha; Hazangwe, Patrick; Choto, Regis C.; Mutasa-Apollo, Tsitsi; Nkomo, Brilliant; Sibanda, Edwin; Mugurungi, Owen; Siziba, Nicholas

    2017-01-01

    Background. In 2013, the tuberculosis (TB) mortality rate was highest in southern Zimbabwe at 16%. We therefore sought to determine factors associated with mortality among registered TB patients in this region. Methodology. This was a retrospective record review of registered patients receiving anti-TB treatment in 2013. Results. Of 1,971 registered TB patients, 1,653 (84%) were new cases compared with 314 (16%) retreatment cases. There were 1,538 (78%) TB/human immunodeficiency virus (HIV) coinfected patients, of whom 1,399 (91%) were on antiretroviral therapy (ART) with median pre-ART CD4 count of 133 cells/uL (IQR, 46–282). Overall, 428 (22%) TB patients died. Factors associated with increased mortality included being ≥65 years old [adjusted relative risk (ARR) = 2.48 (95% CI 1.35–4.55)], a retreatment TB case [ARR = 1.34 (95% CI, 1.10–1.63)], and being HIV-positive [ARR = 1.87 (95% CI, 1.44–2.42)] whilst ART initiation was protective [ARR = 0.25 (95% CI, 0.22–0.29)]. Cumulative mortality rates were 10%, 14%, and 21% at one, two, and six months, respectively, after starting TB treatment. Conclusion. There was high mortality especially in the first two months of anti-TB treatment, with risk factors being recurrent TB and being HIV-infected, despite a high uptake of ART. PMID:28352474

  9. Factors Associated with Mortality among Patients on TB Treatment in the Southern Region of Zimbabwe, 2013.

    PubMed

    Takarinda, Kudakwashe C; Sandy, Charles; Masuka, Nyasha; Hazangwe, Patrick; Choto, Regis C; Mutasa-Apollo, Tsitsi; Nkomo, Brilliant; Sibanda, Edwin; Mugurungi, Owen; Harries, Anthony D; Siziba, Nicholas

    2017-01-01

    Background. In 2013, the tuberculosis (TB) mortality rate was highest in southern Zimbabwe at 16%. We therefore sought to determine factors associated with mortality among registered TB patients in this region. Methodology. This was a retrospective record review of registered patients receiving anti-TB treatment in 2013. Results. Of 1,971 registered TB patients, 1,653 (84%) were new cases compared with 314 (16%) retreatment cases. There were 1,538 (78%) TB/human immunodeficiency virus (HIV) coinfected patients, of whom 1,399 (91%) were on antiretroviral therapy (ART) with median pre-ART CD4 count of 133 cells/uL (IQR, 46-282). Overall, 428 (22%) TB patients died. Factors associated with increased mortality included being ≥65 years old [adjusted relative risk (ARR) = 2.48 (95% CI 1.35-4.55)], a retreatment TB case [ARR = 1.34 (95% CI, 1.10-1.63)], and being HIV-positive [ARR = 1.87 (95% CI, 1.44-2.42)] whilst ART initiation was protective [ARR = 0.25 (95% CI, 0.22-0.29)]. Cumulative mortality rates were 10%, 14%, and 21% at one, two, and six months, respectively, after starting TB treatment. Conclusion. There was high mortality especially in the first two months of anti-TB treatment, with risk factors being recurrent TB and being HIV-infected, despite a high uptake of ART.

  10. Safety and efficacy of daclatasvir in the management of patients with chronic hepatitis C

    PubMed Central

    Manolakopoulos, Spilios; Zacharakis, George; Zissis, Miltiadis; Giannakopoulos, Vassilis

    2016-01-01

    Daclatasvir (Daklinza™), a new oral direct-acting antiviral, is an inhibitor of hepatitis C virus NS5A protein and has recently been approved in the United States, Europe and Japan in chronic hepatitis C. It shows potent pangenotypic activity and moderately high genetic barrier to resistance improving the sustained virological response (SVR) rates. In COMMAND phase 2 trials, daclatasvir demonstrated high SVR rates in HCV genotype 1-4 chronically infected patients treated with peginterferon-a (pegIFNα) plus ribavirin (RBV). Furthermore, it produced even higher response rates in all-oral combination with sofosbuvir, an interferon-free regimen, with or without ribavirin, in patients with advanced liver disease, HCV/HIV coinfection, liver transplantation in ALLY studies and other real-world studies. This narrative review provides information on the pharmacological properties, role, efficacy and safety of daclatasvir-containing regimens in chronic hepatitis C patients. Daclatasvir administered once-daily in combination with sofosbuvir is an effective 12-week treatment in adult patients with chronic hepatitis C and is generally safe and well tolerated. PMID:27366028

  11. Hepatitis B revaccination in healthy non-responder Chinese children: five-year follow-up of immune response and immunologic memory.

    PubMed

    Zhuang, Gui-Hua; Yan, Hong; Wang, Xue-Liang; Hwang, Lu-Yu; Wu, Qian; Wang, Li-Rong; Gao, Hai-Yan

    2006-03-15

    To assess persistence of anti-HBs and immunologic memory of non-responders after revaccination, 40 healthy non-responder children were given a three-dose recombinant hepatitis B vaccine revaccination randomly by intramuscular (10 microg per dose) or intradermal (2 microg per dose) route and followed up to five years. All 17 intramuscular and 22 of 23 intradermal children developed a seroprotective antibody response (anti-HBs>or=10 mIU/mL) after revaccination. Children of intramuscular group had significantly higher seroprotection rates and anti-HBs geometric mean titers than the intradermal group. At year 5, 50% of children in intramuscular group, but only 18.2% of intradermal group still maintained seroprotection (P=0.075). By the end of follow-up, a booster dose (5 microg) was given to those who had lost seroprotection. All the eight intramuscular children developed an anamnestic response with increase of anti-HBs level by 215 times, but two of the 18 intradermal children failed to produce seroprotective level. Three-routine-dose intramuscular revaccination was significantly more effective than low-dose intradermal revaccination with the same number of injections. No child seroconverted to HBsAg, and 11 had transient infections indicated by seroconversion to anti-HBc. These results demonstrated that non-responders could benefit from three doses intramuscular revaccination not only in high proportion of anti-HBs conversion but also in long-term persistence of seroprotection, and more importantly in preservation of the immunologic memory years after loss of protective anti-HBs.

  12. Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine.

    PubMed

    Halperin, Scott A; Ward, Brian J; Dionne, Marc; Langley, Joanne M; McNeil, Shelly A; Smith, Bruce; Mackinnon-Cameron, Donna; Heyward, William L; Martin, J Tyler

    2013-07-01

    An additional one to three doses of hepatitis B vaccine are recommended for nonresponders to an initial standard three-dose series. We compared the safety and immunogenicity of an investigational hepatitis B surface antigen vaccine (HBsAg-1018) with a phosphorothioate oligodeoxyribonucleotide adjuvant that targets toll-like receptor-9 to a commercially available, alum-adjuvanted hepatitis B vaccine (HBsAg-Eng) in nonresponders to three previous doses (primary study) or to four to six previous doses (substudy) of HBsAg-Eng. Both vaccines were well tolerated, although HBsAg-1018 was associated with more injection-site tenderness (63.2% vs. 18.8%, p = 0.016 in the primary study and 81.8% vs. 15.4%, p = 0.003 in the substudy). No statistically significant differences in rates of seroprotection (anti-HBs concentration ≥ 10 mIU/mL) or geometric mean antibody concentrations were found in the primary study. In the substudy, a greater proportion of HBsAg-1018 recipients achieved an anti-HBs concentration ≥ 100 mIU/mL (54.5% vs. 8.3%, p = 0.027), and those responders had higher geometric mean antibody concentrations at 4 weeks (264 vs. 46.5 mIU/mL, p = 0.021) and 52 weeks (7.0 vs. 1.2 mIU/mL, p = 0.030) than HBsAg-Eng recipients. Although this study suggests that HBsAg-1018 may have improved immunogenicity in nonresponders to hepatitis B vaccine vaccination when compared with HBsAg-Eng, larger studies are required.

  13. Low Double-Negative CD3(+)CD4(-)CD8(-) T Cells Are Associated with Incomplete Restoration of CD4(+) T Cells and Higher Immune Activation in HIV-1 Immunological Non-Responders.

    PubMed

    Lu, Xiaofan; Su, Bin; Xia, Huan; Zhang, Xin; Liu, Zhiying; Ji, Yunxia; Yang, Zixuan; Dai, Lili; Mayr, Luzia M; Moog, Christiane; Wu, Hao; Huang, Xiaojie; Zhang, Tong

    2016-01-01

    Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3(+)CD4(-)CD8(-) T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4(+) T cell count. The ART did not result in complete suppression of immune activation recorded by the percentage of CD38(+)HLA-DR(+)CD8(+) T cells in INRs, and a strong inverse correlation was observed between DN T cells and immune activation. A low proportion of TGF-β1(+)DN T cells was found in INRs. Further mechanism study demonstrated that the level of TGF-β1-producing DN T cells and immune activation had a negative correlation after ART. Taken together, our study suggests that DN T cells control the immunological response in HIV-1-infected patients. These findings expand our understanding of the mechanism of immune reconstitution and could develop specific treatments to return the immune system to homeostasis following initiation of HIV-1 therapy.

  14. Low Double-Negative CD3+CD4−CD8− T Cells Are Associated with Incomplete Restoration of CD4+ T Cells and Higher Immune Activation in HIV-1 Immunological Non-Responders

    PubMed Central

    Lu, Xiaofan; Su, Bin; Xia, Huan; Zhang, Xin; Liu, Zhiying; Ji, Yunxia; Yang, Zixuan; Dai, Lili; Mayr, Luzia M.; Moog, Christiane; Wu, Hao; Huang, Xiaojie; Zhang, Tong

    2016-01-01

    Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3+CD4−CD8− T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4+ T cell count. The ART did not result in complete suppression of immune activation recorded by the percentage of CD38+HLA-DR+CD8+ T cells in INRs, and a strong inverse correlation was observed between DN T cells and immune activation. A low proportion of TGF-β1+DN T cells was found in INRs. Further mechanism study demonstrated that the level of TGF-β1-producing DN T cells and immune activation had a negative correlation after ART. Taken together, our study suggests that DN T cells control the immunological response in HIV-1-infected patients. These findings expand our understanding of the mechanism of immune reconstitution and could develop specific treatments to return the immune system to homeostasis following initiation of HIV-1 therapy. PMID:28018346

  15. Brief Report: A High Rate of β7+ Gut-Homing Lymphocytes in HIV-Infected Immunological Nonresponders is Associated With Poor CD4 T-Cell Recovery During Suppressive HAART

    PubMed Central

    Girard, Alexandre; Vergnon-Miszczycha, Delphine; Depincé-Berger, Anne-Emmanuelle; Roblin, Xavier; Lutch, Frederic; Lambert, Claude; Rochereau, Nicolas; Bourlet, Thomas; Genin, Christian

    2016-01-01

    Objective: Correlation between GALT homing markers on lymphocytes and the low blood CD4 T-cell reconstitution in immunological nonresponders (INRs) has been studied. Design: Thirty-one INRs, 19 immunological responders (IRs), and 12 noninfected controls were enrolled in this study. INRs were defined by an undetectable plasma viral load RNA less than 40 copies per milliliter and CD4+ T-cell count <500 cells per cubic milliliter in at least 3 years. Methods: A complete peripheral and mucosal lymphocyte immunophenotyping was performed on these patients with a focus on the CCR9, CCR6, and α4β7 gut-homing markers. Results: A highly significant upregulation of α4β7 on INRs peripheral lymphocytes compared with that of IRs has been observed. This upregulation impacts different lymphocyte subsets namely CD4+, CD8+, and B lymphocytes. The frequency of β7+ Th17 and Treg cells are increased compared with IRs and healthy controls. The frequency of β7+ CD8+ T cells in the blood is negatively correlated with integrated proviral DNA in rectal lymphoid cells in contrast to β7+ CD4+ T cells associated with HIV integration. Conclusions: Alteration of lymphocyte homing abilities would have deleterious effects on GALT reconstitution and could participate to HIV reservoir constitution. These results emphasize the great interest to consider α4β7-targeted therapy in INR patients to block homing of lymphocytes and/or to directly impair gp120-α4β7 interactions. PMID:27306505

  16. Prevalence of serotype D in Cryptococcus neoformans isolates from HIV positive and HIV negative patients in Italy.

    PubMed

    Tortorano, A M; Viviani, M A; Rigoni, A L; Cogliati, M; Roverselli, A; Pagano, A

    1997-11-01

    Cryptococcus neoformans strains isolated from 207 HIV positive and HIV negative patients hospitalized in Northern Italy were serotyped by slide agglutination. One Brazilian HIV negative woman was infected by var. gattii serotype B and all the other patients by var. neoformans, serotype D in 71%, serotype A in 24.6% and serotype AD in 3.4%. No difference was observed between subjects with serotypes A and D in HIV coinfection, exposure categories for AIDS, age, sex, and CD4 count of HIV positive patients. Meningeal and respiratory tract involvements and prostatic reservoir occurred with comparable frequency in AIDS patients infected by serotypes A and D. Skin lesions were observed only in serotype D infections, occurring in 12.6% of HIV positive and 58.3% of HIV negative patients infected by this serotype. Serotype A was found less susceptible to fluconazole than serotype D: 53.7% of serotype A strains had a MIC > or = 25 micrograms ml-1 compared to 17.7% of the serotype D isolates. On the other hand, both serotypes were highly susceptible to itraconazole.

  17. Treatment of chronic hepatitis C in patients with HIV/HCV coinfection

    PubMed Central

    Coppola, Nicola; Martini, Salvatore; Pisaturo, Mariantonietta; Sagnelli, Caterina; Filippini, Pietro; Sagnelli, Evangelista

    2015-01-01

    Hepatitis C virus (HCV) infection is one of the most frequent causes of comorbidity and mortality in the human immunodeficiency virus (HIV) population, and liver-related mortality is now the second highest cause of death in HIV-positive patients, so HCV infection should be countered with adequate antiviral therapy. In 2011 began the era of directly acting antivirals (DAAs) and the HCV NS3/4A protease inhibitors telaprevir and boceprevir were approved to treat HCV-genotype-1 infection, each one in combination with pegylated interferon alfa (Peg-IFN) + ribavirin (RBV). The addition of the first generation DAAs, strongly improved the efficacy of antiviral therapy in patients with HCV-genotype 1, both for the HCV-monoinfected and HIV/HCV coinfected, and the poor response to Peg-IFN + RBV in HCV/HIV coinfection was enhanced. These treatments showed higher rates of sustained virological response than Peg-IFN + RBV but reduced tolerability and adherence due to the high pill burden and the several pharmacokinetic interactions between HCV NS3/4A protease inhibitors and antiretroviral drugs. Then in 2013 a new wave of DAAs arrived, characterized by high efficacy, good tolerability, a low pill burden and shortened treatment duration. The second and third generation DAAs also comprised IFN-free regimens, which in small recent trials on HIV-positive patients have shown comforting preliminary results in terms of efficacy, tolerability and adherence. PMID:25674512

  18. Variability of platelet aggregation in patients with clopidogrel treatment and hip fracture: A retrospective case-control study on 112 patients

    PubMed Central

    Clareus, Anna; Fredriksson, Inga; Wallén, Håkan; Gordon, Max; Stark, André; Sköldenberg, Olof

    2015-01-01

    AIM: To identify the rate of non-responders to clopidogrel treatment in hip fracture patients and study how non-responders differ from controls. METHODS: In a retrospective case-control study we included 28 cases of acute proximal femoral fracture with clopidogrel treatment 2011 to 2013. Eighty-four controls from the same time period were included. Data collected included response to clopidogrel measured with multiple electrode aggregometry (MEA), intraoperative bleeding, erythrocyte transfusion, time to surgery and the incidence of adverse events up to 3 mo after surgery. RESULTS: Eight (29%) of the 28 cases were non-responders. The median intraoperative bleeding was 300 mL (range, 0-1500), and was lower for non-responders (50 mL) but did not reach statistical significance. Erythrocyte transfusions did not differ between responders, non-responders and controls. Forty-five (40%) of 112 patients had adverse events postoperatively but the rate did not differ between patients with and without clopidogrel treatment. CONCLUSION: Almost one-third of patients with clopidogrel treatment and an acute proximal femoral fracture are non-responders to antiplatelet therapy and can be operated without delay. PMID:26085986

  19. Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

    PubMed

    Cacoub, P; Renou, C; Rosenthal, E; Cohen, P; Loury, I; Loustaud-Ratti, V; Yamamoto, A M; Camproux, A C; Hausfater, P; Musset, L; Veyssier, P; Raguin, G; Piette, J C

    2000-01-01

    From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented

  20. Clinical validation of sublingual formulations of Immunoxel (Dzherelo) as an adjuvant immunotherapy in treatment of TB patients.

    PubMed

    Efremenko, Yuri V; Arjanova, Olga V; Prihoda, Natalia D; Yurchenko, Larisa V; Sokolenko, Nina I; Mospan, Igor V; Pylypchuk, Volodymyr S; Rowe, John; Jirathitikal, Vichai; Bourinbaiar, Aldar S; Kutsyna, Galyna A

    2012-03-01

    Immunoxel (Dzherelo) is a water-alcohol extract of medicinal plants used in Ukraine as an adjunct immunotherapy to TB and HIV therapy. Four types of solid sublingual formulations of Immunoxel were made: sugar dragées, sugar-coated pills, gelatin pastilles and dried-honey lozenges. They were administered once-daily along with TB drugs. After 1 month, 84.1% of TB patients became sputum-negative with rates in individual groups of 89.5, 70, 76.9 and 100%, respectively. The conversion rate was independent of bodyweight, age, gender, differences in chemotherapy regimens or whether subjects had newly diagnosed TB, re-treated TB, multidrug-resistant TB or TB with HIV coinfection. Patients experienced earlier clinical improvement, faster defervescence, weight gain, a higher hemoglobin content and reduced inflammation as evidenced by lower leukocyte counts and erythrocyte sedimentation rate. By contrast, in the placebo group, only 19% of patients had converted. These findings imply that mucosal delivery of solid Immunoxel is equivalent to the original liquid formula given per os twice-daily for 2-4 months.

  1. Advance telephone calls ahead of reminder questionnaires increase response rate in non-responders compared to questionnaire reminders only: The RECORD phone trial.

    PubMed

    MacLennan, Graeme; McDonald, Alison; McPherson, Gladys; Treweek, Shaun; Avenell, Alison

    2014-01-08

    Postal questionnaires are simple and economical for collecting outcome data for randomised controlled trials (RCTs) but are prone to non-response. In the RECORD trial (a large pragmatic publicly funded RCT in UK) non-responders were sent a reminder and another questionnaire at 1 year, of which 40% were returned. In subsequent years we investigated the effect of an advance telephone call to non-responders on responses rate to reminder questionnaires and the next questionnaire 4 months later. Non-responders to annual questionnaires were randomised to receive a telephone call from the trial office ahead of the reminder questionnaire in addition to the usual reminder schedule (n=390) or to a control group that received the usual reminder schedule only (n=363). The primary outcome was response to the reminder questionnaire within 21 days; secondary outcomes were response to a questionnaire 4 months later; completeness of quality of life instruments; and the number of participants declining further follow-up. Results are presented as odds ratios from a logistic regression intention-to-treat (ITT) analysis and then percentage difference and 95% confidence intervals (CI) for both ITT and average treatment effect on the treated (ATT) analyses. The proportions that responded were 67.8% (265/390) in the intervention group compared to 62.5% (227/363) in the control group. The ITT estimate was a 5.4% increase (95% CI -1.4 to 12.2). Four months later percentages responding were 51.8% (202) and 42.7% (155). The ITT estimate was a 9.1% increase (95% CI 2.0 to 16.2). In the intervention group 12.3% (48/390) of participants were not telephoned because questionnaires were returned before the scheduled telephone call. ATT estimates adjusting for this were 6.2% (95% CI -1.6 to 14.0) and 10.4% (95% CI 2.2 to 18.5), respectively. The telephone call resulted in a slight increase in response to the reminder questionnaire, however at 4 months later the proportion in the telephoned group

  2. Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine.

    PubMed

    Nyström, Jessica; Cardell, Kristina; Björnsdottir, Thora Björg; Fryden, Aril; Hultgren, Catharina; Sällberg, Matti

    2008-11-05

    We successfully re-vaccinated hepatitis B virus (HBV) vaccine non-responders using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell mediated immune response (CMI) by an increased antigen dose and a theoretical adjuvant-effect from the local presence of a HAV-specific CMI. A few non-responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro detectable HBsAg-specific CMI was primed equally effective in non-responders (58%) as in first time vaccine recipients (68%). After the third dose a weak, albeit significant, association was observed between the magnitude of HBsAg-specific proliferation and anti-HBs levels. This regimen improves the priming of HBsAg-specific CMIs and antibodies.

  3. Ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic hepatitis C and bleeding disorders.

    PubMed

    Walsh, C E; Workowski, K; Terrault, N A; Sax, P E; Cohen, A; Bowlus, C L; Kim, A Y; Hyland, R H; Han, B; Wang, J; Stamm, L M; Brainard, D M; McHutchison, J G; von Drygalski, A; Rhame, F; Fried, M W; Kouides, P; Balba, G; Reddy, K R

    2017-03-01

    Chronic hepatitis C virus (HCV) infection is prevalent among patients with inherited bleeding disorders and is a leading cause of mortality in those with haemophilia. We evaluated the efficacy and safety of ledipasvir-sofosbuvir and sofosbuvir plus ribavirin in patients with chronic HCV genotype 1-4 infection and an inherited bleeding disorder. Ledipasvir-sofosbuvir was administered for 12 weeks to patients with genotype 1 or 4 infection and for 12 or 24 weeks to treatment-experienced cirrhotic patients with genotype 1 infection. Patients with genotype 2 and 3 infection received sofosbuvir plus ribavirin for 12 and 24 weeks respectively. The majority of the 120 treated patients had a severe bleeding disorder (55%); overall, 65% of patients had haemophilia A and 26% of patients had haemophilia B; 22% were HIV coinfected. Sustained virologic response at 12 weeks posttreatment was 99% (98/99) in patients with genotype 1 or 4 infection; 100% (5/5) in treatment-experienced cirrhotic patients with genotype 1 infection; 100% (10/10) in patients with genotype 2 infection; and 83% (5/6) in patients with genotype 3 infection. There were no treatment discontinuations due to adverse events (AEs). The most frequent non-bleeding AEs were fatigue, headache, diarrhoea, nausea and insomnia. Bleeding AEs occurred in 22 patients, of which all but one were considered unrelated to treatment. Treatment with ledipasvir-sofosbuvir for patients with HCV genotype 1 or 4 infection or sofosbuvir plus ribavirin for patients with genotype 2 or 3 infection was highly effective and well tolerated among those with inherited bleeding disorders. © 2017 John Wiley & Sons Ltd.

  4. Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania.

    PubMed

    Drabe, Camilla H; Vestergaard, Lasse S; Helleberg, Marie; Nyagonde, Nyagonde; Rose, Michala V; Francis, Filbert; Theilgaard, Ola P; Asbjørn, Jens; Amos, Ben; Bygbjerg, Ib Christian; Ruhwald, Morten; Ravn, Pernille

    2016-04-01

    Interferon-gamma (IFN-γ) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-γ-inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-γ. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD® In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether-lumefantrine (Coartem®). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN-γ and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-γ and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment. © The American Society of Tropical Medicine and Hygiene.

  5. SECOND-STAGE TREATMENTS FOR RELATIVE NONRESPONDERS TO COGNITIVE BEHAVIORAL THERAPY (CBT) FOR PANIC DISORDER WITH OR WITHOUT AGORAPHOBIA-CONTINUED CBT VERSUS SSRI: A RANDOMIZED CONTROLLED TRIAL.

    PubMed

    Payne, Laura A; White, Kamila S; Gallagher, Matthew W; Woods, Scott W; Shear, M Katherine; Gorman, Jack M; Farchione, Todd J; Barlow, David H

    2016-05-01

    Cognitive behavioral therapy (CBT) and pharmacotherapy are efficacious for the short-term treatment of panic disorder. Less is known about the efficacy of these therapies for individuals who do not respond fully to short-term CBT. The current trial is a second-step stratified randomized design comparing two treatment conditions-selective serotonin reuptake inhibitor (SSRI; paroxetine or citalopram; n = 34) and continued CBT (n = 24)-in a sample of individuals classified as treatment nonresponders to an initial course of CBT for panic disorder. Participants were randomized to 3 months of treatment and then followed for an additional 9 months. Only treatment responders after 3 months were maintained on the treatment until 12-month follow-up. Data analysis focused on panic disorder symptoms and achievement of response status across the first 3 months of treatment. Final follow-up data are presented descriptively. Participants in the SSRI condition showed significantly lower panic disorder symptoms as compared to continued CBT at 3 months. Results were similar when excluding individuals with comorbid major depression or analyzing the entire intent-to-treat sample. Group differences disappeared during 9-month naturalistic follow-up, although there was significant attrition and use of nonstudy therapies in both arms. These data suggest greater improvement in panic disorder symptoms when switching to SSRI after failure to fully respond to an initial course of CBT. Future studies should further investigate relapse following treatment discontinuation for nonresponders who became responders. Clinicaltrials.gov Identifier: NCT00000368; https://clinicaltrials.gov/show/NCT00000368. © 2015 Wiley Periodicals, Inc.

  6. Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy - ACTG A5286.

    PubMed

    Tenorio, Allan R; Chan, Ellen S; Bosch, Ronald J; Macatangay, Bernard J C; Read, Sarah W; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M; Jacobson, Jeffrey M; Landay, Alan L; Wilson, Cara C

    2015-03-01

    Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4(+) T-cell counts <350 cells/mm(3) were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8(+)T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8(+)T-cell activation. Trial registration number. NCT01466595. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Increased Natural Killer Cell Activation in HIV-Infected Immunologic Non-Responders Correlates with CD4+ T Cell Recovery after Antiretroviral Therapy and Viral Suppression

    PubMed Central

    Luo, Zhenwu; Li, Zhen; Martin, Lisa; Hu, Zhiliang; Wu, Hao; Wan, Zhuang; Kilby, Michael; Heath, Sonya L.; Huang, Lei; Jiang, Wei

    2017-01-01

    The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as “immunologic responders” and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as “immunologic non-responders”. We analyzed NK cell number, subset, and activation by expression of CD107a and NKG2D and co-expression of CD38 and HLA-DR. NK cell-mediated cytotoxicity against uninfected CD4+ T cells was tested in vitro. We found that NK cell absolute number, percentage of NK cells, and percentage of NK cell subsets were similar in the three study groups. The increased NK cell activation was found predominantly in CD56dimCD16+ subset of immunologic non-responders but not immunologic responders compared to healthy controls. The activation of NK cells was inversely correlated with the peripheral CD4+ T cell count in HIV+ subjects, even after controlling for chronic T cell activation, sex, and age, potential contributors for CD4+ T cell counts in HIV disease. Interestingly, NK cells from immunologic non-responders mediated cytotoxicity against uninfected CD4+ T cells ex vivo. NK cells may play a role in blunted CD4+ T cell recovery in ART-treated HIV disease. PMID:28076376

  8. Cellular immune responses in multiple sclerosis patients treated with interferon-beta

    PubMed Central

    Bustamante, M. F.; Rio, J.; Castro, Z.; Sánchez, A.; Montalban, X.; Comabella, M.

    2013-01-01

    Summary We investigated cellular immune responses at baseline in peripheral blood mononuclear cells (PBMC) of patients with multiple sclerosis (MS) treated with interferon (IFN)-β and classified into responders and non-responders according to clinical response criteria. Levels for IFN-γ, interleukin (IL)-17A, IL-17F, IL-10 and IL-4 were determined in activated PBMC of 10 responders, 10 non-responders and 10 healthy controls by cytometric bead arrays. Cytokine levels in cell culture supernatants were similar between responders and non-responders, and comparable to those obtained in healthy controls. These findings do not support differential cellular immune responses in PBMC at baseline between IFN-β responders and non-responders. PMID:23379429

  9. Short-term intravenous citalopram augmentation in partial/nonresponders with major depression: a randomized placebo-controlled study.

    PubMed

    Altamura, Alfredo Carlo; Dell'Osso, Bernardo; Buoli, Massimiliano; Bosi, Monica; Mundo, Emanuela

    2008-07-01

    Approximately 30-45% of patients with major depressive episode (MDE) do not fully respond to standard recommended treatments and further strategies of intervention, including pharmacological augmentation, have been proposed for these patients. This study was aimed to evaluate the efficacy of short-term, low-dose (10 mg/day) intravenous (i.v.) citalopram augmentation versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Thirty-six patients with a Diagnostic and Statistical Manual for Mental Disorders, 4th edition, text revision criteria MDE and partial or no response to oral SSRIs were selected and randomly assigned to citalopram (n=18) or to placebo (n=18) i.v. augmentation. The augmentation regimen lasted 5 consecutive days during which the patients were maintained on their current treatment with oral SSRIs. Analyses of variance with repeated measures on Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale total scores, administered daily with blind-raters conditions, were done. With regard to the Hamilton Depression Rating Scale total scores, a significant time effect (F=42.02, P<0.0001) and timextreatment effect (F=21.17, P<0.0001) were found in favor of citalopram. Similar results were obtained from the analysis on Montgomery-Asberg Depression Rating Scale total scores: time effect (F=50.07, P<0.0001), timextreatment effect (F=19.91, P<0.0001), and treatment effect (F=4.07, P=0.05). Even though referred to a small sample, the present findings seem to suggest that short-term, low-dose, i.v. citalopram augmentation may be effective in depressed patients with partial or no response to oral SSRIs. Further controlled studies performed with double-blind conditions are warranted to confirm the present results.

  10. Predominance of Hepatitis B Virus Genotype A Among Treated HIV Infected Patients Experiencing High Hepatitis B Virus Drug Resistance in Nairobi, Kenya.

    PubMed

    Mabeya, Sepha Nyatichi; Ngugi, Caroline; Lihana, Raphael Wekesa; Khamadi, Samoel Ashimosi; Nyamache, Anthony Kebira

    2017-09-01

    Hepatitis B virus (HBV)-HIV coinfections are becoming common with information on HBV genetic diversity and drug resistance still remaining elusive. To evaluate the HBV genetic diversity and drug resistance-associated mutations among drug-experienced HIV patients, the genetic analysis of the partial HBV-pol-reverse trancriptase gene was successfully sequenced from 13 samples. Analysis of the sequences showed that all (11) the sequences belonged to genotype A. Nucleos(t)ide drug resistance mutations were found in 6 patients. Five subjects had rtV173L, rtL180M, and rtM204V and one with rtL180M and rtM204V major mutations. HBV genotype A remains the most predominant genotype circulating in Nairobi city with detected high level of HBV drug resistance to lamivudine, telbivudine, and emtricitabine. The detected circulating HBV genotype A in Nairobi reflects its possible spread in the population with its origin being within the country. We suggest that patients should not be on lamivudine monotherapy. These individuals should be managed on combination of tenofovir plus lamivudine or emtricitabine therapy to prevent the emergence of HBV drug resistant variants alongside a continuous surveillance monitoring of drug resistance and HBV genotypes.

  11. Human T Cell Lymphotropic Virus Type 2a Strains Among HIV Type 1-Coinfected Patients from Brazil Have Originated Mostly from Brazilian Amerindians

    PubMed Central

    Magri, Mariana Cavalheiro; Brigido, Luis Fernando de Macedo; Morimoto, Helena Kaminami

    2013-01-01

    Abstract The human T cell lymphotropic virus type 2 (HTLV-2) is found mainly in Amerindians and in intravenous drug users (IDUs) from urban areas of the United States, Europe, and Latin America. Worldwide, HTLV-2a and HTLV-2b subtypes are the most prevalent. Phylogenetic analysis of HTLV-2 isolates from Brazil showed the HTLV-2a subtype, variant -2c, which spread from Indians to the general population and IDUs. The present study searched for the types of HTLV-2 that predominate among HIV-1-coinfected patients from southern and southeastern Brazil. Molecular characterization of the LTR, env, and tax regions of 38 isolates confirmed the HTLV-2c variant in 37 patients, and one HTLV-2b in a patient from Paraguay. Phylogenetic analysis of sequences showed different clades of HTLV-2 associated with risk factors and geographic region. These clades could represent different routes of virus transmission and/or little diverse evolutionary rates of virus. Taking into account the results obtained in the present study and the lack of the prototypic North American HTLV-2a strain and HTLV-2b subtypes commonly detected among HIV-coinfected individuals worldwide, we could speculate on the introduction of Brazilian HTLV-2 strains in such populations before the introduction of HIV. PMID:23484539

  12. Individual response to neoadjuvant chemotherapy assessed with optical mammography in patients with breast cancer

    NASA Astrophysics Data System (ADS)

    Anderson, Pamela G.; Krishnamurthy, Nishanth; Kalli, Sirishma; Sassaroli, Angelo; Makim, Shital S.; Graham, Roger A.; Fantini, Sergio

    2017-02-01

    We report an optical mammography study on eight patients with breast cancer who underwent neoadjuvant chemotherapy. Of these eight patients, six were responders (tumor size decreased by more than 50%) and two were nonresponders (tumor size decreased by less than 50%). The goals of this study are (1) to characterize the temporal evolution of the hemoglobin concentration ([HbT]) and saturation (SO2) in breast tissue during the course of treatment in responders and non-responders, and (2) to define a quantitative index that is capable of identifying responders and nonresponders during treatment. We found that both [HbT] and SO2 decreased by a greater amount in responders than in non-responders during therapy. This result applied to both cancerous and healthy breast, but the discrimination of responders and non-responders was more significant with SO2 measurements in the cancerous breast. A cumulative response index defined in terms of SO2 measurements in the cancerous breast achieved a 100% sensitivity and 100% specificity for the identification of responders and non-responders at therapy midpoint. These results confirm the potential of optical mammography in assessing response to neoadjuvant chemotherapy during treatment, thus offering the opportunity to consider alternative options to ineffective treatment regimens.

  13. [Clinical, epidemiological and immunological study of patients coinfected with HIV and HTLV-1].

    PubMed

    Scapellato, Pablo G; Bottaro, Edgardo G; Seoane, María B; Rodriguez Brieschke, María T; Scapellato, Jose L; Dato, Adriana; Vidal, Gabriela I

    2004-01-01

    We studied the prevalence of antibodies against HTLV-1 among every HIV-infected outpatients assisted in our hospital between January 1st 2000 and June 30th 2003. We reviewed the epidemiological data, clinical findings, viral load and CD4 cells-count, comparing coinfected with non HTLV-1 coinfected. We found a prevalence of HTLV-1 infection of 8.1% (23/282); 8.5% (12/141) in men and 7.8% (11/141) in women [[OR=0.91 (0.36patients users of illicit drugs and 4.6% (7/152) among non-users [OR=2.93 (1.09patients [p=0.000006 OR=7.42 (2.71patients (96/282) had history of AIDS defining diseases (ADD). No differences in the ADD were found among coinfected and no coinfected patients. No patient developed any disease relative to HTLV-1. The mean of CD4-cells among HTLV-1 coinfected with history of ADD naïve patients (n=7) was 211 cells/ml, and 87.9 cells/ml among those not-coinfected (n=55) [t-test=2.82; p=0.006]. The viral load was similar among every investigated group of patients. We found a high prevalence of HTLV-1 infection in HIV-infected patients (higher among IDU). The CD4-cell count of patients suffering from an AIDS defining disease was higher among HTLV-1/HIV coinfected patients than in singly HIV infected, this could show a grade of missfunction of CD4-cells in coinfected patients.

  14. Clinical course and core variability in HBV infected patients without detectable anti-HBc antibodies.

    PubMed

    Anastasiou, Olympia E; Widera, Marek; Verheyen, Jens; Korth, Johannes; Gerken, Guido; Helfritz, Fabian A; Canbay, Ali; Wedemeyer, Heiner; Ciesek, Sandra

    2017-08-01

    The presence of anti-HBc antibodies indicates direct encounter of the immune system with hepatitis B virus (HBV). Aim of our study was to seek for anti-HBc negative but HBV replicating patients and analyze their clinical course and preconditions. From 1568 HBV-DNA positive patients, 29 patients (1.85%) tested negative for anti-HBc. The absence of anti-HBc could be confirmed in 19 patients using an alternative assay. In 16 of 19 cases, a partial or full HBV genome analysis was performed with NGS sequencing to evaluate if specific mutations were associated with anti-HBc absence. As a control group samples from 32 matched HBV infected patients with detectable anti-HBc were sequenced. Patients with detectable HBV-DNA and sequenced HBV core region in the confirmed absence of anti-HBc were diagnosed with acute HBV infection (n=3), HBV reactivation (n=9) and chronic hepatitis B (n=4). Most patients (12/16) were immunosuppressed: 3/16 patients had an HIV coinfection, 7/16 patients suffered from a malignant disease and 4/16 patients underwent solid organ transplantation (from which 2/4 had a malignant disease). Compared to the control cohort, HBV variants from anti-HBc negative patients showed less variability in the core region. In the absence of anti-HBc, HBV-DNA was most often found in immunocompromised hosts. Distinct mutations or deletions in the core region did not explain anti-HBc negativity. It would be advisable not to rely only on a single result of anti-HBc negativity to exclude HBV infection in immunocompromised hosts, but to measure anti-HBc repeatedly or with different methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Relationship Between HIV Coinfection, Interleukin 10 Production, and Mycobacterium tuberculosis in Human Lymph Node Granulomas

    PubMed Central

    Diedrich, Collin R.; O'Hern, Jennifer; Gutierrez, Maximiliano G.; Allie, Nafiesa; Papier, Patricia; Meintjes, Graeme; Coussens, Anna K.; Wainwright, Helen; Wilkinson, Robert J.

    2016-01-01

    Background. Human immunodeficiency virus type 1 (HIV)–infected persons are more susceptible to tuberculosis than HIV–uninfected persons. Low peripheral CD4+ T-cell count is not the sole cause of higher susceptibility, because HIV–infected persons with a high peripheral CD4+ T-cell count and those prescribed successful antiretroviral therapy (ART) remain more prone to active tuberculosis than HIV–uninfected persons. We hypothesized that the increase in susceptibility is caused by the ability of HIV to manipulate Mycobacterium tuberculosis–associated granulomas. Methods. We examined 71 excised cervical lymph nodes (LNs) from persons with HIV and M. tuberculosis coinfection, those with HIV monoinfection, and those with M. tuberculosis monoinfection with a spectrum of peripheral CD4+ T-cell counts and ART statuses. We quantified differences in M. tuberculosis levels, HIV p24 levels, cellular response, and cytokine presence within granulomas. Results. HIV increased M. tuberculosis numbers and reduced CD4+ T-cell counts within granulomas. Peripheral CD4+ T-cell depletion correlated with granulomas that contained fewer CD4+ and CD8+ T cells, less interferon γ, more neutrophils, more interleukin 10 (IL-10), and increased M. tuberculosis numbers. M. tuberculosis numbers correlated positively with IL-10 and interferon α levels and fewer CD4+ and CD8+ T cells. ART reduced IL-10 production. Conclusions. Peripheral CD4+ T-cell depletion correlated with increased M. tuberculosis presence, increased IL-10 production, and other phenotypic changes within granulomas, demonstrating the HIV infection progressively changes these granulomas. PMID:27462092

  16. Population Pharmacokinetics of Rifampin in Pregnant Women with Tuberculosis and HIV Coinfection in Soweto, South Africa

    PubMed Central

    Denti, Paolo; Martinson, Neil; Cohn, Silvia; Mashabela, Fildah; Hoffmann, Jennifer; Msandiwa, Reginah; Castel, Sandra; Wiesner, Lubbe; Chaisson, Richard E.; McIlleron, Helen

    2015-01-01

    Effective treatment of tuberculosis during pregnancy is essential for preventing maternal and fetal mortality, but little is known about the effects of pregnancy on the disposition of antituberculosis drugs. We explored the effects of pregnancy on the pharmacokinetics of rifampin, the key sterilizing drug in tuberculosis treatment, in Tshepiso, a prospective cohort study involving pregnant HIV-infected women with or without tuberculosis in Soweto, South Africa. Participants receiving standard first-line tuberculosis treatment underwent sparse sampling for rifampin at 37 weeks' gestation or delivery and then postpartum. Cord blood was collected when possible. A population pharmacokinetic model was developed to investigate the effects of pregnancy on rifampin pharmacokinetics. Among the 48 participants, median age and weight were 28 years and 67 kg, respectively. A one-compartment model with first-order elimination, transit compartment absorption, and allometric scaling described the data well. Pregnancy reduced rifampin clearance by 14%. The median (interquartile range) model-estimated rifampin area under the concentration-time curve over 24 h (AUC0–24) during pregnancy or intrapartum was 40.8 h · mg/liter (27.1 to 54.2 h · mg/liter) compared to 37.4 h · mg/liter (26.8 to 50.3 h · mg/liter) postpartum. The maximum concentrations were similar during pregnancy and postpartum. Rifampin was detectable in 36% (8/22) of cord blood samples, and 88% (42/48) of the women had successful treatment outcomes. There was one case of perinatal tuberculosis. In conclusion, rifampin clearance is modestly reduced during the last trimester of pregnancy. Exposures are only slightly increased, so dose adjustment during pregnancy is not needed. Rifampin was detected in cord blood samples when delivery occurred soon after dosing. The consequences of exposure to this potent inducer of metabolizing enzymes among HIV-exposed infants are unclear. PMID:26643345

  17. Population Pharmacokinetics of Rifampin in Pregnant Women with Tuberculosis and HIV Coinfection in Soweto, South Africa.

    PubMed

    Denti, Paolo; Martinson, Neil; Cohn, Silvia; Mashabela, Fildah; Hoffmann, Jennifer; Msandiwa, Reginah; Castel, Sandra; Wiesner, Lubbe; Chaisson, Richard E; McIlleron, Helen; Dooley, Kelly E

    2015-12-07

    Effective treatment of tuberculosis during pregnancy is essential for preventing maternal and fetal mortality, but little is known about the effects of pregnancy on the disposition of antituberculosis drugs. We explored the effects of pregnancy on the pharmacokinetics of rifampin, the key sterilizing drug in tuberculosis treatment, in Tshepiso, a prospective cohort study involving pregnant HIV-infected women with or without tuberculosis in Soweto, South Africa. Participants receiving standard first-line tuberculosis treatment underwent sparse sampling for rifampin at 37 weeks' gestation or delivery and then postpartum. Cord blood was collected when possible. A population pharmacokinetic model was developed to investigate the effects of pregnancy on rifampin pharmacokinetics. Among the 48 participants, median age and weight were 28 years and 67 kg, respectively. A one-compartment model with first-order elimination, transit compartment absorption, and allometric scaling described the data well. Pregnancy reduced rifampin clearance by 14%. The median (interquartile range) model-estimated rifampin area under the concentration-time curve over 24 h (AUC0-24) during pregnancy or intrapartum was 40.8 h · mg/liter (27.1 to 54.2 h · mg/liter) compared to 37.4 h · mg/liter (26.8 to 50.3 h · mg/liter) postpartum. The maximum concentrations were similar during pregnancy and postpartum. Rifampin was detectable in 36% (8/22) of cord blood samples, and 88% (42/48) of the women had successful treatment outcomes. There was one case of perinatal tuberculosis. In conclusion, rifampin clearance is modestly reduced during the last trimester of pregnancy. Exposures are only slightly increased, so dose adjustment during pregnancy is not needed. Rifampin was detected in cord blood samples when delivery occurred soon after dosing. The consequences of exposure to this potent inducer of metabolizing enzymes among HIV-exposed infants are unclear.

  18. Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence.

    PubMed

    Vidal, Júlia Souza; Silva, Marcus Tolentino; Sanchez, Mauro Niskier

    2015-01-01

    Latent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

  19. IL28B rs12980275 polymorphism shows association with response to treatment in Pakistani patients with chronic hepatitis C.

    PubMed

    Shaikh, Naila; Waryah, Ali Muhammad; Devrajani, Bikha Ram; Rajput, Muhammad Irfan; Hayat, Atif Sitwat; Shaikh, Samiullah

    2015-05-01

    The aim of this study was to describe the genetic characteristics of Pakistani patients infected with hepatitis C virus (HCV) in relation to IL28B polymorphisms and its association to interferon and ribavirin treatment response. A total of 220 patients, infected with HCV were enrolled, out of which 100 were responders and 120 were nonresponders. The whole blood samples were collected to extract viral RNA and genomic DNA. PCR following the restriction fragment length polymorphism method was used to genotype IL28B rs12979860, rs8099917, and rs12980275 polymorphisms. Liver biopsies and HCV genotyping were performed in nonresponder patients. The rs12980275 AA genotype exhibited significant correlation to treatment response and was found in 62% of the responders and 37.5% of nonresponder patients, whereas AG genotype was noticed frequently in the nonresponder group (P < 0.0001). The rs12979860 CT and rs8099917 TT genotypes were found in 74% and 66% of the responders as compared to 58.3% and 50.8% in nonresponder patients (P = 0.001 and P = 0.032) respectively. HCV 3a genotypes were detected in 50.8% of the nonresponder patients. No significant association was detected between liver biopsy findings and IL28B SNPs (P > 0.05). The results showed the significant association of rs12980275 polymorphism with treatment response in HCV patients followed by rs12979860 and rs8099917. This is the first report describing the association of rs12980275 with response to HCV treatment from Pakistan. These findings may help in predicting the outcome of pegylated interferon and ribavirin treatment in HCV patients, and may reduce the side effects and cost of treatment in predicting non-responder patients. © 2015 Wiley Periodicals, Inc.

  20. Improvement in sexual functioning and satisfaction in nonresponders to testosterone gel: clinical effectiveness in hypogonadal, HIV-positive males.

    PubMed

    Schrader, Shannon; Mills, Anthony; Scheperle, Mark; Block, Jon E

    2005-01-01

    Impairment in gonadal function with reduced testosterone (T) levels is commonly associated with HIV infection and patients often complain of diminished libido and sexual dysfunction. The effectiveness of Testim 1% (Auxilium Pharmaceuticals, Inc., Norristown, Pennsylvania) topical T gel was evaluated in HIV-positive males who failed to experience satisfactory symptom relief following prior treatment with AndroGel 1% (Solvay Pharmaceuticals, Inc., Marietta, Georgia). In this open-label study, consecutive subjects were randomly assigned to experimental treatment with Testim 1% (5 g) or to maintenance therapy (control group) with AndroGel 1% (5 g). Twenty-four experimental subjects and 24 control subjects were followed for 4 weeks to evaluate improvements in sexual functioning and satisfaction. Changes from baseline in the 5 domains of the Brief Male Sexual Function Inventory (BMSFI) were compared between groups. The average percentage improvement favored the experimental treatment in all 5 comparisons of the BMSFI, including sexual drive (53% vs 18%, P < 0.001), erectile function (49% vs 7%, P < 0.004), ejaculatory function (15% vs 8%, P < 0.14), problem assessment (59% vs 12%, P < 0.003), and sexual satisfaction (58% vs 9%, P < 0.006). A greater percentage of subjects also reported satisfaction with the experimental treatment (85% vs 48%, P < 0.03), and these subjects were less likely to require upward dose titration at the final follow-up visit (30% vs 74%, P = 0.01). It is hypothesized that the results of the current study may be explained, in part, by an improved pharmacokinetic profile of the experimental intervention. Consideration of Testim 1% gel in HIV patients who have an inadequate response to prior T therapy is encouraged, although it is difficult to estimate the contribution of nonspecific study effects (eg, placebo) in this trial.

  1. Social constraints to TB/HIV healthcare: accounts from coinfected patients in South Africa.

    PubMed

    Daftary, Amrita; Padayatchi, Nesri

    2012-01-01

    There is a growing imperative to improve the coordination and collaboration of tuberculosis (TB) and HIV healthcare services in response to escalating rates of TB/HIV coinfection. Patient-specific challenges associated with the delivery of TB/HIV care have been minimally explored in this regard. As part of a larger study conducted in South Africa, this article highlights coinfected patients' experiences with TB and HIV healthcare in light of their broader social environments. Qualitative, in-depth interviews were conducted with 40 adult, coinfected patients (24 women and 16 men) and eight key-informant healthcare workers at three urban/peri-urban, ambulatory, public health clinics in the high-burden province of KwaZulu-Natal. Transcribed interviews were analyzed under a modified grounded theory approach to capture subjective meanings of healthcare experience subsequent to patients' codiagnosis with TB and HIV. Emerging analytic themes highlighted critical sociomedical constraints to TB/HIV care in relation to patients' income and employment, eligibility for social assistance and antiretroviral treatment, fears around illness disclosure, social and material support, and treatment adherence. Patients' healthcare experiences were bound by their poor access to essential resources, multiple life responsibilities, disparate gender roles, limits within the healthcare system, and the stigmatizing social symbolism of their illness. Overlapping social inequalities perpetuated coinfected patients' experiences with stigma and collectively mediated their health decisions around disclosure, adherence, and retention in medical care. The study urges a contextualized understanding of the social challenges associated with TB/HIV healthcare and helps inform more patient-sensitive and socially responsive interventions against the co-epidemic.

  2. Comparing recidivism rates of treatment responders/nonresponders in a sample of 413 child molesters who had completed community-based sex offender treatment in the United kingdom.

    PubMed

    Beech, Anthony R; Mandeville-Norden, Rebecca; Goodwill, Alasdair

    2012-02-01

    Analysis of psychometric data from a sample of 413 child molesters who had completed a U.K. probation-based sex offender treatment program was carried out to assess (a) the effectiveness of therapy in the short term and (b) the longer term implications of treatment in relation to sexual recidivism. It was found that 12% (51 offenders) of the sample had recidivated within 2 to 4 years. Of these recidivists, 86% (44 offenders) had been reconvicted for a sexually related offense. One hundred thirty-five offenders (33%) demonstrated a treated profile (i.e., demonstrated no offense-specific problems and few, or no, socioaffective problems at the posttreatment stage). This group was compared with a sample of offenders deemed as not responding to treatment, matched by their levels of pretreatment risk/need. It was found that a significantly smaller proportion (n = 12, 9%) of treatment responders had recidivated, compared to the treatment nonresponders (n = 20, 15%), indicating a 40% reduction in recidivism in those who had responded to treatment (effect size = .18). Matching length of treatment to the offenders' level of pretreatment risk/need (i.e., higher risk/treatment-need offenders typically undertook longer treatment) reduced the rate of recidivism among this group to the level of recidivism observed among the lower risk/need offenders.

  3. Increased hepatocyte fas expression and apoptosis in HIV and hepatitis C virus coinfection.

    PubMed

    Macias, Juan; Japón, Miguel A; Sáez, Carmen; Palacios, Rosa B; Mira, José A; García-García, José A; Merchante, Nicolás; Vergara, Salvador; Lozano, Fernando; Gómez-Mateos, Jesús; Pineda, Juan A

    2005-11-01

    Chronic hepatitis C disease (CHC) follows an accelerated course in human immunodeficiency virus (HIV) coinfection. The reasons for this are unclear. Fas-mediated hepatocyte apoptosis is involved in the pathogenesis of hepatitis C virus (HCV) infection. We sought to compare the expression of Fas on hepatocytes and irreversible apoptosis of hepatocytes among patients with CHC with and without HCV/HIV coinfection. Fas-immunostained hepatocytes were semiquantified, and apoptotic hepatocytes were detected by staining caspase-cleaved cytokeratin 18 filaments and counted across the entire section of liver-biopsy specimens from HCV-infected patients with and without HCV/HIV coinfection. One hundred thirty-four HCV/HIV-coinfected and 100 HCV-infected patients were included. HCV/HIV coinfection was associated with both diffuse distribution of Fas-stained hepatocytes (adjusted odds ratio [AOR], 7.4 [95% confidence interval {CI}, 3.8-14.4]) and with apoptotic hepatocyte counts greater than the median (AOR, 2.5 [95% CI, 1.5-4.5]). In HCV/HIV-coinfected patients, CD4+ cell nadir<200 cells/mL was associated with both Fas expression (AOR, 2.9 [95% CI, 1.3-6.8]) and hepatocyte apoptosis (AOR, 2.3 [95% CI, 1.1-4.9]). HCV/HIV-coinfected patients show higher levels of hepatocytes expressing Fas and undergoing irreversible apoptosis than do HCV-infected patients. However, low CD4+ cell nadirs in coinfected patients are associated with hepatocyte Fas expression and apoptosis.

  4. [The National Danish Survey of Patient Experiences has a small positive bias].

    PubMed

    Rosenstjerne Andersen, Angelo; Fuglsang, Marie; Kyed, Daisy

    2012-10-01

    The response rate in The National Danish Survey of Patient Experiences in 2009 was 54%. In order to evaluate bias due to non-responders, The Unit of Patient-perceived Quality merged survey data and data on patient background from Statistics Denmark. The relationships between the responding patients' background and their answers to six questions in the survey questionnaire are estimated with logistic regression analysis and subsequently used for predicting the answers of the non-responders. Results indicate a small positive bias in four of the questions and no bias in the remaining two.

  5. Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial.

    PubMed

    Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

    2017-04-01

    Our aim was to investigate the effects and prevalence of nonresponders (NR) to high-intensity interval training (HIIT) and resistance training (RT) in women with insulin resistance on cardiometabolic health parameters. Sedentary overweight/obese insulin-resistant women (age = 33.5 ± 6.5 yr; body mass index = 29.9 ± 3.7 kg/m(2)) were randomly assigned to a triweekly HIIT program (HIIT; n = 18) or resistance training (RT; n = 17). Anthropometry (body mass, fat mass, muscle mass, waist circumference, and skinfold thickness), cardiovascular (blood pressure), metabolic [fasting glucose, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR)], as well as muscle strength, and endurance performance covariables were measured before and after 12 wk in both intervention groups. The interindividual variability to exercise training of the subjects was categorized as responders and NR using as cut points two times the typical error of measurement in mean outcomes. After intervention, significant reduction in waist circumference, skinfold thicknesses, fat mass, blood pressure, fasting glucose, insulin, and HOMA-IR (P < 0.05) were identified to HIIT and RT group, respectively. Both HIIT and RT groups exhibited a significant decrease in the endurance performance, whereas only RT exhibited increased muscle strength. Significant differences in the NR prevalence between the HIIT and RT groups were identified for a decrease in fat mass (HIIT 33.3% vs. RT 70.5%; P = 0.028), muscle mass (HIIT 100% vs. RT 52.9%; P = 0.001), and tricipital skinfold (HIIT 5.5% vs. RT 29.4%; P < 0.041). For diastolic blood pressure, significant differences were observed in the NR prevalence between the HIIT and RT groups (55.5% vs. 94.1; P = 0.009). However, there were no differences in the NR prevalence between HIIT and RT for decreasing fasting glucose. Twelve weeks of HIIT and RT have similar effects and NR prevalence to improve glucose control variables; however, there is different NR

  6. Dominant enrichment of phenotypically activated CD38(+) HLA-DR(+) CD8(+) T cells, rather than CD38(+) HLA-DR(+) CD4(+) T cells, in HIV/HCV coinfected patients on antiretroviral therapy.

    PubMed

    d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Serafino, Sara; Giustini, Noemi; Cavallari, Eugenio Nelson; Bianchi, Luigi; Pavone, Paolo; Bellelli, Valeria; Turriziani, Ombretta; Antonelli, Guido; Stroffolini, Tommaso; Vullo, Vincenzo

    2016-08-01

    HIV infection may enhance immune-activation, while little is known regarding the role of HCV infection. This study investigates the impact of HCV in HIV coinfected patients with undetectable viraemia under HAART on the levels of peripheral T cell's immune-activation. We determined T lymphocytes subsets to characterize immune-activation defined as CD38 and/or HLA-DR expression in chronic monoinfected HCV, HIV, and HIV/HCV coinfected subjects. One hundred and fifty six patients were divided into three groups: (i) 77 HIV+ patients; (ii) 50 HCV+ patients; and (iii) 29 coinfected HIV/HCV patients. The level of CD4(+) was significantly higher in HCV+ than in HIV+ or in coinfected HIV/HCV subjects. The frequencies of CD4(+) CD38(+) /HLA-DR(-) , CD4(+) CD38(-) /HLA-DR(+) and CD4(+) CD38(+) /HLA-DR(+) in HIV+ patients were comparable to those measured in coinfected patients, but statistically higher than those observed in HCV+ subjects. The percentage of CD8(+) was comparable in HIV-1+ patients and coinfected HIV/HCV but the results obtained in both groups were significantly higher compared to the results obtained in HCV patients. The level of CD8(+) CD38(+) /HLA-DR(-) showed values lower in HIV+ patients than in that monoinfected HCV and coinfected HIV/HCV patients. The frequencies of CD8(+) CD38(-) /HLA-DR(+) were higher in HIV+ patients compared to HCV+ and coinfected HIV/HCV patients. HIV/HCV coinfected group showed highest levels of CD8(+) CD38(+) /HLA-DR(+) . HIV plays a pivotal role to determine the immune activation in the host. The role of HCV needs of further investigations but our data show that HCV mainly influences the immune-activation of the pool of CD8, but also probably plays a supporting additive effect on CD4 immune-activation. J. Med. Virol. 88:1347-1356, 2016. © 2016 Wiley Periodicals, Inc.

  7. Clinical Features of Human Immunodeficiency Virus-Infected Patients Presenting with Cholera in Port-au-Prince, Haiti.

    PubMed

    Sévère, Karine; Anglade, Stravinsky B; Bertil, Claudin; Duncan, Aynsley; Joseph, Patrice; Deroncenay, Alexandra; Mabou, Marie M; Ocheretina, Oksana; Reif, Lindsey; Seo, Grace; Pape, Jean W; Fitzgerald, Daniel W

    2016-11-02

    Human immunodeficiency virus (HIV) infection has been postulated to alter the natural history of cholera, including increased susceptibility to infection, severity of illness, and chronic carriage of Vibrio cholerae Haiti has a generalized HIV epidemic with an adult HIV prevalence of 1.9% and recently suffered a cholera epidemic. We conducted a prospective study at the cholera treatment center (CTC) of GHESKIO in Haiti to characterize the coinfection. Adults admitted at the CTC for acute diarrhea were invited to participate in the study. Vital signs, frequency, and volume of stools and/or vomiting were monitored, and single-dose doxycycline was administered. After counseling, participants were screened for HIV by enzyme-linked immunosorbent assay and for cholera by culture. Of 729 adults admitted to the CTC, 99 (13.6%) had HIV infection, and 457 (63%) had culture-confirmed cholera. HIV prevalence was three times higher in patients without cholera (23%, 63/272) than in those with culture-confirmed cholera (7.9%, 36/457). HIV prevalence in patients with culture-confirmed cholera (7.9%) was four times higher than the adult prevalence in Port-au-Prince (1.9%). Of the 36 HIV-infected patients with cholera, 25 (69%) had moderate/severe dehydration versus 302/421 (72%) in the HIV negative. Of 30 HIV-infected patients with weekly stool cultures performed after discharge, 29 (97%) were negative at week 1. Of 50 HIV-negative patients with weekly stool cultures, 49 (98%) were negative at week 1. In countries with endemic HIV infection, clinicians should consider screening patients presenting with suspected cholera for HIV coinfection.

  8. Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance.

    PubMed

    Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

    2017-01-01

    Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R) or non-responders (NRs), especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT) and the prevalence of NRs in adult women with higher and lower levels of insulin resistance. Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m(2); n = 20) and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m(2); n = 20). Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training. Results: There were significant training-induced changes [delta percent (Δ%)] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores in the H-IR group (-8.8, -26.5, -32.1%, p < 0.0001), whereas no significant changes were observed in the L-IR. Both groups showed significant pre-post changes in other anthropometric variables [waist circumference (-5.2, p < 0.010, and -3.8%, p = 0.046) and tricipital (-13.3, p < 0.010, and -13.6%, p < 0.0001), supra-iliac (-19.4, p < 0.0001, and -13.6%, p < 0.0001), and abdominal (-18.2, p < 0.0001, and -15.6%, p < 0.010) skinfold measurements]. Systolic blood pressure decreased significantly only in the L-IR group (-3.2%, p < 0.010). Both groups showed significant increases in 1RMLE (+12.9, p < 0.010, and +14.7%, p = 0.045). There were significant differences in the prevalence of NRs between the H-IR and L-IR groups for fasting glucose (25 vs. 95%, p < 0.0001) and fasting insulin (p = 0.025) but not for HOMA-IR (25 vs. 45%, p = 0.185). Conclusion: Independent of the "magnitude" of the cardiometabolic disease (i

  9. Risk factors for multidrug-resistant tuberculosis among tuberculosis patients: a case-control study

    PubMed Central

    Workicho, Abdulhalik; Kassahun, Wondwosen; Alemseged, Fessahaye

    2017-01-01

    Background Multidrug-resistant tuberculosis (MDR-TB) did not receive major attention until recently in sub-Saharan Africa where the tuberculosis incidence and risk factors are highest. Factors leading to development of drug resistance need to be understood to develop appropriate control strategies for national programs. The objective of this study was to identify the risk factors for MDR-TB among tuberculosis patients. Methods A case-control study was conducted to assess sociodemographic, behavioral and clinical risk factors using a structured questionnaire and clinical record reviewing. The data were entered and analyzed using SPSS windows version 16. Descriptive analysis was done to generate summary values for the variables and those significant variables in the bivariate analysis at p-value less than 0.25 were entered to multivariable logistic regression to identify independent determinants. Statistical significance was declared at p-value less than or equal to 0.05. Results A total of 90 cases and 90 controls were included in the study. Age of respondents (adjusted odds ratio [AOR] =7; 95% confidence interval [CI]: 2.6–24.5), living in a household with only one room (AOR=5; 95%CI: 1.68–15.38), history of previous treatment (AOR=21; 95% CI: 17.8–28) and being HIV infected (AOR=3.1; 95%CI: 1.02–9.4) were found to be independent predictors of MDR-TB. Conclusion In light of these findings, the strategies in controlling MDR-TB should emphasize on patients with HIV coinfection, young patients, those who have a history of previous treatment, and those living in crowded places. PMID:28331350

  10. Assessment of isoniazid preventive therapy in the reduction of tuberculosis among ART patients in Arba Minch Hospital, Ethiopia.

    PubMed

    Abossie, Ashenafi; Yohanes, Tsegaye

    2017-01-01

    Tuberculosis (TB) is the most frequent life-threatening opportunistic disease among people living with HIV and remains a leading cause of mortality, even among persons receiving antiretroviral therapy (ART). Isoniazid preventive therapy (IPT) and cotrimoxazole prophylaxis have been recommended for the benefit of HIV/AIDS-infected individuals to prevent opportunistic infections. The aim of this study was to assess IPT prophylaxis in the reduction of TB among ART patients. The study was a hospital-based retrospective study. A total of 271 study participants' available information such as demographic data, the type of prophylaxis used, and TB/HIV coinfection status as well as other variables were collected from clinical laboratory and HIV care/ART follow-up clinic. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 20.0. TB-infected ART patients were higher among non-IPT group (37 [27.8%]) compared to IPT group (12 [8.7%]). The finding showed that IPT prophylaxis significantly reduces acquiring TB with the relative risk =0.31 (95% confidence interval =0.122, 0.49) in ART patients of this study site where the tuberculosis prevalence is prominent. ART had significant contribution for CD4(+) T-cell lymphocyte count improvement in both IPT and non-IPT groups (P<0.05) in this study. IPT had significant contributions to reduce the burden of TB in ART patients than non-IPT group. This result highlights the use of IPT for the prevention of TB, especially for all ART patients. Other longitudinal studies are needed to observe the benefits and side effects of IPT prophylaxis in tuberculin skin test-positive individuals.

  11. Assessment of isoniazid preventive therapy in the reduction of tuberculosis among ART patients in Arba Minch Hospital, Ethiopia

    PubMed Central

    Abossie, Ashenafi; Yohanes, Tsegaye

    2017-01-01

    Background Tuberculosis (TB) is the most frequent life-threatening opportunistic disease among people living with HIV and remains a leading cause of mortality, even among persons receiving antiretroviral therapy (ART). Isoniazid preventive therapy (IPT) and cotrimoxazole prophylaxis have been recommended for the benefit of HIV/AIDS-infected individuals to prevent opportunistic infections. The aim of this study was to assess IPT prophylaxis in the reduction of TB among ART patients. Methods The study was a hospital-based retrospective study. A total of 271 study participants’ available information such as demographic data, the type of prophylaxis used, and TB/HIV coinfection status as well as other variables were collected from clinical laboratory and HIV care/ART follow-up clinic. Data analysis was performed using Statistical Package for the Social Sciences (SPSS) version 20.0. Results TB-infected ART patients were higher among non-IPT group (37 [27.8%]) compared to IPT group (12 [8.7%]). The finding showed that IPT prophylaxis significantly reduces acquiring TB with the relative risk =0.31 (95% confidence interval =0.122, 0.49) in ART patients of this study site where the tuberculosis prevalence is prominent. ART had significant contribution for CD4+ T-cell lymphocyte count improvement in both IPT and non-IPT groups (P<0.05) in this study. Conclusion IPT had significant contributions to reduce the burden of TB in ART patients than non-IPT group. This result highlights the use of IPT for the prevention of TB, especially for all ART patients. Other longitudinal studies are needed to observe the benefits and side effects of IPT prophylaxis in tuberculin skin test-positive individuals. PMID:28392698

  12. UGT1A1∗28 relationship with abnormal total bilirubin levels in chronic hepatitis C patients

    PubMed Central

    de Souza, Marcelo Moreira Tavares; Vaisberg, Victor Van; Abreu, Rodrigo Martins; Ferreira, Aline Siqueira; daSilvaFerreira, Camila; Nasser, Paulo Dominguez; Paschoale, Helena Scavone; Carrilho, Flair José; Ono, Suzane Kioko

    2017-01-01

    Abstract Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1∗28 (UGT1A1∗28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions’ to the liver disease scenario. Our aim was to assess UGT1A1 genotypes’ frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case–control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)–polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients. Genotypes and alleles frequencies were similar in case (n = 585; P = 0.101) and control groups (n = 313; P = 0.795). Total bilirubin increase was noticed according to thymine–adenine repeats in genotypes (P < 0.001), and the TB greater than 1 mg/dL group had more UGT1A1∗28 subjects than in the group with TB values <1 mg/dL (18.3 vs 5.3; P < 0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A1∗28 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism. PMID:28296739

  13. Efficacy of and risk of bleeding during pegylated interferon plus ribavirin treatment in HIV/HCV-coinfected patients with pretreatment thrombocytopenia.

    PubMed

    Mira, J A; Neukam, K; López-Cortés, L F; Rivero-Juárez, A; Téllez, F; Girón-González, J A; de los Santos-Gil, I; Ojeda-Burgos, G; Merino, D; Ríos-Villegas, M J; Collado, A; Torres-Cornejo, A; Macías, J; Rivero, A; Pérez-Pérez, M; Pineda, J A

    2015-09-01

    The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm(3) and >70,000/mm(3), respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm(3). The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm(3) in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm(3) in the platelet >70,000 group (p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR (p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population.

  14. Abacavir does not influence the rate of virological response in HIV-HCV-coinfected patients treated with pegylated interferon and weight-adjusted ribavirin.

    PubMed

    Laufer, Natalia; Laguno, Montserrat; Perez, Iñaki; Cifuentes, Carmen; Murillas, Javier; Vidal, Francesc; Bonet, Lucia; Veloso, Sergio; Gatell, José María; Mallolas, Josep

    2008-01-01

    The combination of pegylated interferon (PEG-IFN) plus ribavirin (RBV) is the standard of care for hepatitis C virus (HCV) treatment in HIV-coinfected individuals. In 2007, abacavir (ABC)-based antiretroviral therapy was, for the first time, reported to be associated with early virological failure during HCV treatment. The aim of our study was to evaluate the effect of ABC on the response rate to HCV therapy. A retrospective analysis of HIV-HCV-coinfected patients treated with PEG-IFN and weight-adjusted RBV in four hospitals in Spain was performed. An analysis of baseline descriptive variables was conducted. Logistic regression models were used to test possible associations between non-response and pretreatment characteristics, including antiretroviral drugs. A total of 244 HIV-HCV-coinfected patients treated with PEG-IFN and RBV were included. Overall, 85% of patients were on highly active antiretroviral therapy; of these patients, 24% received ABC-based regimens. The most frequent genotypes were 1 and 3. RBV dosing was 213.2 mg/kg/day in 97% of the patients. In the global intent-to-treat analyses, 46.3% of patients reached a sustained virological response (SVR; 46.2% in ABC group versus 46.7% in non-ABC group, P=1). The only two factors in the multivariate analysis that were statistically associated with an increased risk of failure to achieve SVR were HCV genotypes 1 or 4 and older age. The use of ABC was not associated with failure to achieve SVR at any of the other time points evaluated. Our data suggest that the use of ABC-based regimens in the context of HCV therapy does not negatively affect the outcome of this treatment.

  15. Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance

    PubMed Central

    Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

    2017-01-01

    Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R) or non-responders (NRs), especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT) and the prevalence of NRs in adult women with higher and lower levels of insulin resistance. Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m2; n = 20) and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m2; n = 20). Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training. Results: There were significant training-induced changes [delta percent (Δ%)] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores in the H-IR group (−8.8, −26.5, −32.1%, p < 0.0001), whereas no significant changes were observed in the L-IR. Both groups showed significant pre-post changes in other anthropometric variables [waist circumference (−5.2, p < 0.010, and −3.8%, p = 0.046) and tricipital (−13.3, p < 0.010, and −13.6%, p < 0.0001), supra-iliac (−19.4, p < 0.0001, and −13.6%, p < 0.0001), and abdominal (−18.2, p < 0.0001, and −15.6%, p < 0.010) skinfold measurements]. Systolic blood pressure decreased significantly only in the L-IR group (−3.2%, p < 0.010). Both groups showed significant increases in 1RMLE (+12.9, p < 0.010, and +14.7%, p = 0.045). There were significant differences in the prevalence of NRs between the H-IR and L-IR groups for fasting glucose (25 vs. 95%, p < 0.0001) and fasting insulin (p = 0.025) but not for HOMA-IR (25 vs. 45%, p = 0.185). Conclusion: Independent of the “magnitude” of the

  16. Changes in CD4+ T-cells and HIV RNA resulting from combination of anti-TB therapy with Dzherelo in TB/HIV dually infected patients

    PubMed Central

    Nikolaeva, Lyudmila G; Maystat, Tatyana V; Masyuk, Lilia A; Pylypchuk, Volodymyr S; Volyanskii, Yuri L; Kutsyna, Galyna A

    2008-01-01

    The open-label, phase II clinical trial of antituberculosis therapy (ATT) with or without oral immunomodulator Dzherelo (Immunoxel) was conducted in TB/HIV coinfected, antiretroviral therapy naïve patients to evaluate the effect on CD4 T-lymphocyte counts and viral load. The arm A (n = 20) received isoniazid (H); rimfapicin (R); pyrazinamide (Z); streptomycin (S); and ethambutol (E), and arm B (n = 20) received 50 drops of Dzherelo twice per day in addition to HRZSE. After 2 months in 90% of Dzherelo patients the population of absolute CD4 T-cells expanded by an average of 71.2% (from 174 to 283 cells/μl; P = 0.00003), but declined in ATT-alone patients (182 to 174; P = 0.34). The ratio between CD4/CD8 cells deteriorated in 80% of individuals in arm A (1.213 > 0.943; P = 0.002), but improved in the same proportion of patients in arm B (1.244 > 1.536; P = 0.007). The number of total CD3+ lymphocytes rose from 728 to 921 cells in arm B (P = 0.025) whereas it fell from 650 to 585 cells in arm A (P = 0.25). The viral load, as measured by plasma RNA-PCR, decreased in 70% of Dzherelo recipients (2.174 > 1.558 copies/ml; P = 0.002), but increased in 70% of HRZSE only receivers (1.907 > 2.076 copies/ml; P = 0.03). Dzherelo has a favorable effect on the immune status and viral burden in TB/HIV patients when given as an immunomodulating adjunct to ATT. PMID:19920896

  17. Hepatitis C virus long-term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1.

    PubMed

    Parodi, C; García, G; Monzani, M C; Culasso, A; Aloisi, N; Corti, M; Campos, R; de E de Bracco, M M; Baré, P

    2015-07-01

    Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.

  18. TLR7 Gln11Leu single nucleotide polymorphism and response to treatment with imiquimod in patients with basal cell carcinoma: a pilot study.

    PubMed

    Piaserico, Stefano; Michelotto, Anna; Frigo, Anna C; Alaibac, Mauro

    2015-11-01

    The Toll-like receptor 7 (TLR7) agonist, imiquimod, offers a topical and noninvasive therapeutic method for the clinical treatment of superficial basal cell carcinoma (BCC). In this study we explored the relationship between the functional X-linked TLR7 rs179008/Gln11Leu polymorphism and the response to imiquimod in patients with BCC. Thirty-four BCC patients treated with imiquimod were included in the study. SNP genotyping of the TLR7 promoter polymorphism was performed by TaqMan allelic discrimination assay. In the group of female nonresponders to imiquimod a higher frequency of the altered genotype compared with responders was observed. Similarly, in the group of male nonresponders to imiquimod both patients with the mutated genotype were nonresponders. The results of this study show that patients carrying at least one T allele of the TLR7 promoter polymorphism are associated with an increased probability to be resistant to imiquimod therapy.

  19. Immune response gene control of collagen reactivity in man: collagen unresponsiveness in HLA-DR4 negative nonresponders is due to the presence of T-dependent suppressive influences

    SciTech Connect

    Solinger, A.M.; Stobo, J.D.

    1982-11-01

    To determine whether the failure to detect collagen reactivity in nonresponders represents an absence of collagen-reactive T cells or a preponderance of suppressive influences, the peripheral blood mononuclear cells from HLA-DR4/sup -/ individuals were subjected to three procedures capable of separating suppressive influences from LIF-secreting cells; irradiation (1000 rad), discontinuous gradient fractionation, and cytolysis with the monoclonal antibody OKT 8. Each procedure resulted in the specific appearance of reactivity to collagen, which was identical to that seen in HLA-DR4/sup +/ individuals with regard to its cellular requirements and antigenic specificity. Addition of unresponsive (i.e., nonirradiated or low-density T cells) to responsive (i.e., irradiated or high-density T cells) autologous populations resulted in specific suppression of collagen reactivity. Radiation-sensitive suppressive influences could not be detected in HLA-DR4/sup +/ collagen responders.These studies indicate that the expression of T-dependent reactivity to collagen in man reflects the net influence of collage-reactive vs collagen-suppressive T cells. Moreover, it is the influence of HLA-D-linked genes on the development of suppressive influences rather than on the development of collagen-reactive, LIF-secreting T cells that serves to distinguish HLA-DR4/sup +/ collagen responders from HLA-DR4/sup -/ collagen nonresponders. (JMT)

  20. Rifaximin has a Marginal Impact on Microbial Translocation, T-cell Activation and Inflammation in HIV-Positive Immune Non-responders to Antiretroviral Therapy – ACTG A5286

    PubMed Central

    Tenorio, Allan R.; Chan, Ellen S.; Bosch, Ronald J.; Macatangay, Bernard J. C.; Read, Sarah W.; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M.; Jacobson, Jeffrey M.; Landay, Alan L.; Wilson, Cara C.; Mellors, John W.; Keshavarzian, Ali; Rodriguez, Benigno; Aziz, Mariam; Presti, Rachel; Deeks, Steven; Ebiasah, Ruth; Myers, Laurie; Borowski, LuAnn; Plants, Jill; Palm, David A.; Weibel, Derek; Putnam, Beverly; Lindsey, Elizabeth; Player, Amy; Albrecht, Mary; Kershaw, Andrea; Sax, Paul; Keenan, Cheryl; Walton, Patricia; Baum, Jane; Stroberg, Todd; Hughes, Valery; Coster, Laura; Kumar, Princy N.; Yin, Michael T.; Noel-Connor, Jolene; Tebas, Pablo; Thomas, Aleshia; Davis, Charles E.; Redfield, Robert R.; Sbrolla, Amy; Flynn, Teri; Davis, Traci; Whitely, Kim; Singh, Baljinder; Swaminathan, Shobha; McGregor, Donna; Palella, Frank; Aberg, Judith; Cavanagh, Karen; Santana Bagur, Jorge L.; Flores, Olga Méndez; Fritsche, Janice; Sha, Beverly; Slamowitz, Debbie; Valle, Sandra; Tashima, Karen; Patterson, Helen; Harber, Heather; Para, Michael; Eaton, Molly; Maddox, Dale; Currier, Judith; Cajahuaringa, Vanessa; Luetkemeyer, Annie; Dwyer, Jay; Fichtenbaum, Carl J.; Saemann, Michelle; Ray, Graham; Campbell, Thomas; Fischl, Margaret A.; Bolivar, Hector; Oakes, Jonathan; Chicurel-Bayard, Miriam; Tripoli, Christine; Weinman, D. Renee; Adams, Mary; Hurley, Christine; Dunaway, Shelia; Storey, Sheryl; Klebert, Michael; Royal, Michael

    2015-01-01

    Background. Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). Methods. HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4+ T-cell counts <350 cells/mm3 were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Results. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8+T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. Conclusions. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8+T-cell activation. Trial registration number. NCT01466595. PMID:25214516

  1. Mutations in the E2 and NS5A regions in patients infected with hepatitis C virus genotype 1a and their correlation with response to treatment.

    PubMed

    Yahoo, Neda; Sabahi, Farzaneh; Shahzamani, Kiana; Malboobi, Mohamad Ali; Jabbari, Hossain; Sharifi, Houshang; Mousavi-Fard, Seyed Hossein; Merat, Shahin

    2011-08-01

    Heterogeneity of subgenomic regions of hepatitis C virus (HCV) may be associated with response to interferon (IFN) therapy. The amino acid sequences of the PKR/eIF-2α phosphorylation homology domain (pePHD), IFN sensitivity determining region (ISDR), PKR binding domain (PKRBD), and variable region 3 (V3) were studied in 19 patients before and after 4 weeks of treatment. All patients were infected with HCV genotype 1a and were treated with pegylated-IFN and ribavirin. Thirteen patients achieved sustained viral response (responders) and six failed to clear viral RNA (nonresponders). The amino acid sequences in the pePHD and ISDR were identical in responders and nonresponders. However, amino acid substitution at position 2252 of PKRBD was significantly different between responders and nonresponders (P = 0.044). A larger number of mutations were observed in the V3 region of responders (P < 0.001). In this region, the amino acid in position 2364 differed between responders and nonresponders (responders: aspartic acid and serine, nonresponders: asparagine, P = 0.018). The amino acid sequences in the regions which were studied did not change after 4 weeks of treatment. It is concluded that the presence of specific amino acids in position 2252 of PKRBD and position 2364 of V3 might be associated with clinical response to IFN. Copyright © 2011 Wiley-Liss, Inc.

  2. Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform.

    PubMed

    Bush, Jacob T; Wasunna, Monique; Alves, Fabiana; Alvar, Jorge; Olliaro, Piero L; Otieno, Michael; Sibley, Carol Hopkins; Strub Wourgaft, Nathalie; Guerin, Philippe J

    2017-09-01

    There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL) annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult. Individual Participant Data (IPD) files can be standardised and analysed, allowing detailed analysis of this merged larger pool, but only a small fraction of systematic reviews and meta-analyses currently employ pooled analysis of IPD. We conducted a systematic literature review to identify published studies and studies reported in clinical trial registries to assess the feasibility of developing a VL data sharing platform to facilitate an IPD-based analysis of clinical trial data. Studies conducted between 1983 to 2015 that reported treatment outcome were eligible. From the 2,271 documents screened, 145 published VL clinical trials were identified, with data from 26,986 patients. Methodologies varied for diagnosis and treatment outcomes, but overall the volume of data potentially available on different drugs and dose regimens identified hundreds or possibly thousands of patients per arm suitable for IPD pooled meta-analyses. A VL data sharing platform would provide an opportunity to maximise scientific use of available data to enable assessment of treatment efficacy, contribute to evidence-based clinical management and guide optimal prospective data collection.

  3. National profile and treatment outcomes of patients with extrapulmonary tuberculosis in Bénin.

    PubMed

    Ade, Serge; Harries, Anthony D; Trébucq, Arnaud; Ade, Gabriel; Agodokpessi, Gildas; Adjonou, Christine; Azon, Sophie; Anagonou, Sévérin

    2014-01-01

    In sub-Saharan Africa, there is a dearth of published literature on extrapulmonary tuberculosis (EPTB). To describe demographic, diagnostic and HIV-status characteristics of patients with EPTB in Bénin, their treatment outcomes, and among those who completed their treatment in the Centre National Hospitalier de Pneumo-Phtisiologie (CNHP-P), the proportion whose bodyweight increased during treatment. This was a retrospective cohort study with comparisons made between EPTB and new smear-positive pulmonary tuberculosis (NPTB) patients diagnosed in the country from January to December 2011. There were 383 EPTB patients (9% of all TB cases) with a mean age of 35 years, male/female ratio of 1.3 and important regional variation. There were significantly more females (p = 0.001), children <15 years (p<0.001) and HIV-positive patients (p = 0.005) with EPTB compared with NPTB. Pleural effusion, spinal and lymph node tuberculosis accounted for 66% of all EPTB. Children <15 years represented 16% of cases, with lymph node disease being most common among them (p<0.001). Of 130 EPTB patients registered in CNHP-P, 7% had a confirmed bacteriological/histological diagnosis. There were 331 (86%) patients who successfully completed treatment. More patients with EPTB were lost-to-follow-up compared with NPTB (p<0.001) with all these patients from one region. The best treatment completion rates were in children <15 years (OR:3.5, 95%CI:1.0-14.8) while patients with pleural effusion and ascites had the worst outcomes. Of 72 HIV-coinfected patients, 88% were on antiretroviral therapy (ART). HIV-positive status was associated with poor outcomes while those on ART fared better. In the CNHP-P, more than 80% who completed their treatment showed an increase in bodyweight and this was more evident in HIV-positive compared with HIV-negative patients (p = 0.03). Patients with EPTB generally do well in Bénin, although the TB Programme would benefit through more attention to accurate

  4. Use of a 12 months' self-referral reminder to facilitate uptake of bowel scope (flexible sigmoidoscopy) screening in previous non-responders: a London-based feasibility study.

    PubMed

    Kerrison, Robert S; McGregor, Lesley M; Marshall, Sarah; Isitt, John; Counsell, Nicholas; Wardle, Jane; von Wagner, Christian

    2016-03-29

    In March 2013, NHS England extended its national Bowel Cancer Screening Programme to include 'one-off' Flexible Sigmoidoscopy screening (NHS Bowel Scope Screening, BSS) for men and women aged 55. With less than one in two people currently taking up the screening test offer, there is a strong public health mandate to develop system-friendly interventions to increase uptake while the programme is rolling out. This study aimed to assess the feasibility of sending a reminder to previous BSS non-responders, 12 months after the initial invitation, with consideration for its potential impact on uptake. This study was conducted in the ethnically diverse London Boroughs of Brent and Harrow, where uptake is below the national average. Between September and November 2014, 160 previous non-responders were randomly selected to receive a reminder of the opportunity to self-refer 12 months after their initial invitation. The reminder included instructions on how to book an appointment, and provided options for the time and day of the appointment and the gender of the endoscopist performing the test. To address barriers to screening, the reminder was sent with a brief locally tailored information leaflet designed specifically for this study. Participants not responding within 4 weeks were sent a follow-up reminder, after which there was no further intervention. Self-referral rates were measured 8 weeks after the delivery of the follow-up reminder and accepted as final. Of the 155 participants who received the 12 months' reminder (returned to sender, n=5), 30 (19.4%) self-referred for an appointment, of which 24 (15.5%) attended and were successfully screened. Attendance rates differed by gender, with significantly more women attending an appointment than men (20.7% vs 8.8%, respectively; OR=2.73, 95% CI=1.02-7.35, P=0.05), but not by area (Brent vs Harrow) or area-level deprivation. Of the 30 people who self-referred for an appointment, 27 (90%) indicated a preference for a same

  5. Slow CD4+ T-Cell Recovery in Human Immunodeficiency Virus/Hepatitis B Virus-Coinfected Patients Initiating Truvada-Based Combination Antiretroviral Therapy in Botswana

    PubMed Central

    Anderson, Motswedi; Gaseitsiwe, Simani; Moyo, Sikhulile; Thami, Kerapetse P.; Mohammed, Terence; Setlhare, Ditiro; Sebunya, Theresa K.; Powell, Eleanor A.; Makhema, Joseph; Blackard, Jason T.; Marlink, Richard; Essex, Max; Musonda, Rosemary M.

    2016-01-01

    Background. Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection has emerged as an important cause of morbidity and mortality. We determined the response to Truvada-based first-line combination antiretroviral therapy (cART) in HIV/HBV-coinfected verus HIV-monoinfected patients in Botswana. Methods. Hepatitis B virus surface antigen (HBsAg), HBV e antigen (HBeAg), and HBV deoxyribonucleic acid (DNA) load were determined from baseline and follow-up visits in a longitudinal cART cohort of Truvada-based regimen. We assessed predictors of HBV serostatus and viral suppression (undetectable HBV DNA) using logistic regression techniques. Results. Of 300 participants, 28 were HBsAg positive, giving an HIV/HBV prevalence of 9.3% (95% confidence interval [CI], 6.3–13.2), and 5 of these, 17.9% (95% CI, 6.1–36.9), were HBeAg positive. There was a reduced CD4+ T-cell gain in HIV/HBV-coinfected compared with HIV-monoinfected patients. Hepatitis B virus surface antigen and HBeAg loss was 38% and 60%, respectively, at 24 months post-cART initiation. The HBV DNA suppression rates increased with time on cART from 54% to 75% in 6 and 24 months, respectively. Conclusions. Human immunodeficiency virus/HBV coinfection negatively affected immunologic recovery compared with HIV-1C monoinfection. Hepatitis B virus screening before cART initiation could help improve HBV/HIV treatment outcomes and help determine treatment options when there is a need to switch regimens. PMID:27800524

  6. Prediction of short-term changes in symptom severity by baseline plasma homovanillic acid levels in schizophrenic patients receiving clozapine.

    PubMed

    Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

    1997-03-24

    The relationship between pretreatment levels of plasma homovanillic acid (pHVA) and the outcome of clozapine treatment was studied in 18 male patients with schizophrenia who were resistant to treatment with conventional neuroleptics. After 6 months of clozapine treatment, 7 patients demonstrated > or = 20% decrease in the Brief Psychiatric Rating Scale (BPRS) (responders), while 11 patients did not (non-responders). Responders and non-responders did not differ with respect to the baseline pHVA level. The BPRS Positive Symptom scores at 6 weeks and 3 months, but not those at baseline and 6 months, following initiation of clozapine treatment negatively correlated with pHVA levels for all patients. The correlations became stronger when only responders were included. No significant correlation between Positive Symptom scores and pHVA levels was observed for non-responders. The BPRS Total and Negative Symptom scores did not correlate with pHVA for all patients, responders or non-responders at any time. The percent decrease in the BPRS Positive Symptom scores from baseline at 6 weeks following clozapine treatment correlated significantly with pHVA levels in responders. These results suggest that pretreatment levels of pHVA can be used to predict relatively short-term changes in the positive symptoms of patients with schizophrenia receiving clozapine treatment, particularly for clozapine responders.

  7. The place of additional individual psychotherapy in the treatment of alcoholism: a randomized controlled study in nonresponders to anticraving medication-results of the PREDICT study.

    PubMed

    Berner, Michael M; Wahl, Sonja; Brueck, Rigo; Frick, Katrin; Smolka, Robert; Haug, Monika; Hoffmann, Sabine; Reinhard, Iris; Leménager, Tagrid; Gann, Horst; Batra, Anil; Mann, Karl

    2014-04-01

    Goal of the presented study is to evaluate whether alcohol-dependent patients given additional individual psychotherapy after a heavy relapse during pharmacotherapy remain abstinent for longer than those who continue with pharmacotherapy alone. In a randomized, multicenter study, 109 alcohol-dependent patients who had suffered a heavy relapse either while receiving anticraving medication or placebo were randomized into 2 groups. One group received medication, medical management, and additional individual, disorder-specific, cognitive-behavioral psychotherapy, while the control group received medication and medical management only. Main outcome was defined as days until first heavy relapse. Fifty-four patients were randomized to the psychotherapy group, 55 to the control group. Intention-to-treat and completer analyses found no differences between groups, whereas as-treated analyses (patients who actually received psychotherapy compared with those who did not) found a significant effect of psychotherapy. Our data indicate that patients that are willing to attend psychotherapy benefit from receiving psychotherapy in addition to pharmacotherapy. We suggest that it may be beneficial to consider patients' preferences concerning psychotherapy at an earlier stage during treatment. Copyright © 2013 by the Research Society on Alcoholism.

  8. Three months of weekly rifapentine and isoniazid for treatment of Mycobacterium tuberculosis infection in HIV-coinfected persons.

    PubMed

    Sterling, Timothy R; Scott, Nigel A; Miro, Jose M; Calvet, Guilherme; La Rosa, Alberto; Infante, Rosa; Chen, Michael P; Benator, Debra A; Gordin, Fred; Benson, Constance A; Chaisson, Richard E; Villarino, M Elsa

    2016-06-19

    Compare the effectiveness, tolerability, and safety of 3 months of weekly rifapentine and isoniazid under direct observation (3HP) versus 9 months of daily isoniazid (9H) in HIV-infected persons. Prospective, randomized, and open-label noninferiority trial. The United States , Brazil, Spain, Peru, Canada, and Hong Kong. HIV-infected persons who were tuberculin skin test positive or close contacts of tuberculosis cases. 3HP versus 9H. The effectiveness endpoint was tuberculosis; the noninferiority margin was 0.75%. The tolerability endpoint was treatment completion; the safety endpoint was drug discontinuation because of adverse drug reaction. Median baseline CD4 cell counts were 495 (IQR 389-675) and 538 (IQR 418-729) cells/μl in the 3HP and 9H arms, respectively (P = 0.09). In the modified intention-to-treat analysis, there were two tuberculosis cases among 206 persons [517 person-years (p-y) of follow-up] in the 3HP arm (0.39 per 100 p-y) and six tuberculosis cases among 193 persons (481 p-y of follow-up) in the 9H arm (1.25 per 100 p-y). Cumulative tuberculosis rates were 1.01 versus 3.50% in the 3HP and 9H arms, respectively (rate difference: -2.49%; upper bound of the 95% confidence interval of the difference: 0.60%). Treatment completion was higher with 3HP (89%) than 9H (64%) (P < 0.001), and drug discontinuation because of an adverse drug reaction was similar (3 vs. 4%; P = 0.79) in 3HP and 9H, respectively. Among HIV-infected persons with median CD4 cell count of approximately 500 cells/μl, 3HP was as effective and safe for treatment of latent Mycobacterium tuberculosis infection as 9H, and better tolerated.

  9. PknE, a serine/threonine protein kinase of Mycobacterium tuberculosis initiates survival crosstalk that also impacts HIV coinfection.

    PubMed

    Parandhaman, Dinesh Kumar; Hanna, Luke Elizabeth; Narayanan, Sujatha

    2014-01-01

    Serine threonine protein kinases (STPK) play a major role in the pathogenesis of Mycobacterium tuberculosis. Here, we examined the role of STPK pknE, using a deletion mutant ΔpknE in the modulation of intracellular signaling events that favor M. tuberculosis survival. Phosphorylation kinetics of MAPK (p38MAPK, Erk½ and SAPK/JNK) was defective in ΔpknE compared to wild-type infected macrophages. This defective signaling dramatically delayed and reduced the phosphorylation kinetics of transcription factors ATF-2 and c-JUN in ΔpknE infected macrophages. MAPK inhibitors instead of reducing the phosphorylation in ΔpknE infected macrophages, revealed crosstalks with Erk½ signaling influenced by SAPK/JNK and p38 pathways independently. Modulations in intra cellular signaling altered the expression of coreceptors CCR5 and CXCR4 in ΔpknE infected macrophages. In conclusion, pknE plays a role in MAPK crosstalks that enables intracellular survival of M. tuberculosis. This survival strategy also impacts HIV/TB coinfection.

  10. High-amplitude left ventricular pacing in cardiac resynchronization therapy: an alternative way to increase response rate in non-responders

    PubMed Central

    Akın, Filiz; Demircan, Sabri; Soylu, Korhan; Erbay, Alirıza; Yuksel, Serkan; Meric, Murat; Gulel, Okan; Sahin, Mahmut; Yılmaz, Ozcan

    2013-01-01

    Purpose This study compared patients who underwent cardiac resynchronization therapy (CRT) by high-amplitude left ventricular (LV) pacing with those who underwent CRT by standard LV pacing. Methods We included 32 CRT patients with ejection fraction (EF) ≤35%, QRS time ≥120 ms, and New York Heart Association (NYHA) class III/IV symptoms of heart failure despite optimal medical treatment. These patients were evaluated clinically and echocardiographically before, three and six months after CRT. At the 3rd month, the LV pulse amplitude value was set high at 5 volt for 16 patients [high-amplitude Group (HAG)], while for the other 16 patients, it was reduced to at least twice the threshold value at ≤2.5 volt [low-amplitude group (LAG)]. Results Clinical and echocardiographic response rates of HAG and LAG after CRT were similar in the 3rd and 6th month. In both groups, increase in LVEF and decrease in LV ESV in the 3rd and 6th month were statistically significant compared to those before CRT, and NYHA class and end-diastolic volume (EDV) was significantly reduced in the 6th month compared to those before CRT. However, NHYA class and EDV continued to reduce significantly in HAG from the 3rd to the 6th month (P<0.05), while the decrease in LAG was not significant (P>0.05). The rate of mitral regurgitation (MR) was reduced significantly in HAG in the 6th month compared to that before CRT, while the decrease in LAG was not significant (P<0.05; P>0.05 respectively). Conclusions CRT by high-amplitude LV pacing was more effective according to clinical and echocardiographic evaluations. It should be considered as an alternative in non-responsive patients. PMID:24255779

  11. Interleukin 1-Beta (IL-1β) Production by Innate Cells Following TLR Stimulation Correlates With TB Recurrence in ART-Treated HIV-Infected Patients.

    PubMed

    Thobakgale, Christina; Naidoo, Kewreshini; McKinnon, Lyle R; Werner, Lise; Samsunder, Natasha; Karim, Salim Abdool; Ndungʼu, Thumbi; Altfeld, Marcus; Naidoo, Kogieleum

    2017-02-01

    Tuberculosis (TB) remains a major cause of global morbidity and mortality, especially in the context of HIV coinfection because immunity is not completely restored following antiretroviral therapy (ART). The identification of immune correlates of risk for TB disease could help in the design of host-directed therapies and clinical management. This study aimed to identify innate immune correlates of TB recurrence in HIV+ ART-treated individuals with a history of previous successful TB treatment. Twelve participants with a recurrent episode of TB (cases) were matched for age, sex, time on ART, pre-ART CD4 count with 12 participants who did not develop recurrent TB in 60 months of follow-up (controls). Cryopreserved peripheral blood mononuclear cells from time-points before TB recurrence were stimulated with ligands for Toll-like receptors (TLR) including TLR-2, TLR-4, and TLR-7/8. Multicolor flow cytometry and intracellular cytokine staining were used to detect IL-1β, TNF-α, IL-12, and IP10 responses from monocytes and myeloid dendritic cells (mDCs). Elevated production of IL-1β from monocytes following TLR-2, TLR-4, and TLR-7/8 stimulation was associated with reduced odds of TB recurrence. In contrast, production of IL-1β from both monocytes and mDCs following Bacillus Calmette-Guérin (BCG) stimulation was associated with increased odds of TB recurrence (risk of recurrence increased by 30% in monocytes and 42% in mDCs, respectively). Production of IL-1β by innate immune cells following TLR and BCG stimulations correlated with differential TB recurrence outcomes in ART-treated patients and highlights differences in host response to TB.

  12. Cost-minimization analysis of treprostinil vs. epoprostenol as an alternate to oral therapy non-responders for the treatment of pulmonary arterial hypertension.

    PubMed

    Narine, L; Hague, L K; Walker, J H; Vicente, C; Schilz, R; Desjardins, O; Einarson, T R; Iskedjian, M

    2005-12-01

    Idiopathic pulmonary arterial hypertension (IPAH) is associated with substantial morbidity and mortality. Treprostinil was compared to epoprostenol for the economic impact of treating IPAH patients who failed or were not candidates for bosentan. The model was a cost-minimization analysis, assuming clinical equivalence was achieved by proper dosing of both drugs, in terms of survival and surrogate measures. Two theoretical cohorts of 270 patients were treated with subcutaneous treprostinil and intravenous epoprostenol, and were evaluated over 3 years using a spreadsheet model. Annual survival rates were estimated for the cohorts so that at endpoint 114 (42%) patients survived in both groups. The model utilized resource valuation data for medication and supply costs from Medicare; hospital, consultation, surgical, and diagnostic procedural fees from North Carolina hospitals; and costs to treat adverse events from published sources. Costs were obtained from standard lists and were presented as 2003 US dollars, discounted at 3%. Sensitivity analyses were performed testing all model uncertainties. In the base case analysis, treprostinil demonstrated savings of 22,701 US dollars and 37,433 US dollars per patient over 1- and 3-year time horizons, respectively. The greatest savings came from reduced or minimal hospitalizations attributed to the dose titration and treatment of adverse events, such as sepsis, associated with epoprostenol and its delivery system. Probabilistic sensitivity analyses resulted in average 3-year cost-savings of 41,051 US dollars (Standard Deviation = 13,902 US dollars) per patient. By initiating and continuing treatment with treprostinil over a 3-year period, the economic burden associated with IPAH may be reduced compared to treatment with epoprostenol. The greatest saving with treprostinil was attributed to decreased sepsis.

  13. Defective antigen presentation by monocytes in ESRD patients not responding to hepatitis B vaccination: impaired HBsAg internalization and expression of ICAM-1 and HLA-DR/Ia molecules

    PubMed Central

    Barth, C.; Pollok, M.; Michałkiewicz, J.; Madaliński, K.; Maciejewski, J.; Baldamis, C. A.

    1995-01-01

    This study was undertaken to evaluate the monocyte function of uraemic non-responders to hepatitis B vaccination. Therefore, some parameters concerning antigen processing by monocytes (Mo) as antigen presenting cells (APC) were analysed. It was found that in uraemic non-responders, (1) the internalization of HBsAg by monocytes was significantly decreasjed—HBsAg complexed with specific IgG or as immune complex isolated from patients is better internalized compared with free HBsAg; (2) during antigen presentation the expression of adhesion (ICAM-1) and accessory (HLA-DR/Ia) molecules was significantly decreased in uraemic patients, especially in non-responders; and (3) impaired internalization of HBsAg as well as a decrease in ICAM-1 and HLA-DR/Ia expression, correlated well with the blunted proliferation of CD4+ T cells stimulated by autologous monocytes induced by HBsAg. PMID:18475616

  14. Actigraphic assessment of periodic leg movements in patients with restless legs syndrome.

    PubMed

    Cippà, Maria A T; Baumann, Christian R; Siccoli, Massimiliano M; Bassetti, Claudio L; Poryazova, Rositsa; Werth, Esther

    2013-10-01

    The diagnosis of restless legs syndrome (RLS) relies upon diagnostic criteria which are based on history only, and dopaminergic treatment is not normally the first choice of treatment for all patients. It would be worthwhile to identify patients non-responsive to dopaminergic treatment beforehand, because they may suffer from a restless legs-like syndrome and may require alternative treatment. We included retrospectively 24 adult patients fulfilling the four essential criteria for restless legs and 12 age-matched healthy controls. They were investigated by ambulatory actigraphy from both legs over three nights, and patients started treatment with dopamine agonists after this diagnostic work-up. We examined 12 responders to dopaminergic treatment and 12 non-responders and studied the association between response to dopaminergic treatment and the periodic limb movement index (PLMI) as assessed with actigraphy. Demographic characteristics, excessive daytime sleepiness and fatigue at baseline were similar in all three groups. Baseline RLS severity was similar between responders and non-responders [International Restless Legs Severity Scale (IRLS): 25 ± 9 and 24 ± 8]. Group comparisons of PLMI before treatment initiation showed significant differences between the three groups. Post-hoc pairwise comparisons revealed that healthy controls had significantly lower PLMI (4.9 ± 4.5) than responders (29.3 ± 22.7) and non-responders (13.3 ± 11.2). Similarly, the PLMI in responders was lower than in non-responders. PLMI day-to-day variability did not differ between responders and non-responders and there was no correlation between treatment effect, as assessed by the decrease of the IRLS and baseline PLMI. Our retrospective study indicates that actigraphy to assess periodic limb movements may contribute to a better diagnosis of dopamine-responsive restless legs syndrome.

  15. Influence of striatal dopamine transporter availability on the response to methylphenidate in adult patients with ADHD.

    PubMed

    Krause, Johanna; la Fougere, Christian; Krause, Klaus-Henning; Ackenheil, Manfred; Dresel, Stefan H

    2005-12-01

    In this study, we investigated whether availability of striatal dopamine transporter (DAT) may have an influence on the response of adult patients with attention deficit hyperactivity disorder (ADHD) on methylphenidate (MPH). In 18 non-smoking and non-medicated adult patients with ADHD, availability of DAT was measured with [(99m)Tc] TRODAT-1 SPECT. Then, the patients received methylphenidate (MPH), individually titrated up to 60 mg per day. Ten weeks later, clinical improvement was rated by Clinical Global Impressions scale. In all, 6 patients were classified as non-responders, and 12 responded to MPH. From the non-responders, 5 presented with a DAT availability below that of normal controls of the same age, whereas in the group of responders all patients had elevated DAT availability. There was a significant negative correlation between values for global clinical improvement and striatal DAT availability. In conclusion, ADHD patients with low DAT availability seem not to respond to therapy with MPH.

  16. Mycobacterium tuberculosis and human immunodeficiency virus coinfection in a tertiary care hospital in Midwestern Brazil.

    PubMed

    Lins, Tatiana Bacelar Acioli; Soares, Eldom de Medeiros; dos Santos, Felipe Macedo; Mandacaru, Polyana Maria Pimenta; Pina, Tatiana; de Araújo Filho, João Alves

    2012-06-01

    Infection with human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB), and HIV TB coinfection is associated with higher mortality. This study aimed to characterize patients coinfected with Mycobacterium tuberculosis and HIV in a reference centre for cases involving complications or drug resistance in TB. This retrospective cohort study was conducted at a Hospital for Tropical Diseases in the state of Goiás, Midwestern Brazil. Patients' medical records were reviewed between January 2008 and December 2009. Sixty-one cases of TB/HIV coinfection were evaluated, and 54 HIV-seronegative TB cases were selected as controls. The prevalence of TB HIV coinfected patients in 2008/2009 was 23%. Coinfection was more prevalent in men (75.4%), with a mean age of 37.1 years. Pulmonary disease (50.8%) was the most frequent clinical form of TB in coinfected patients, followed by disseminated disease (32.8%). Anaemia, malnutrition and low levels of CD4 T lymphocytes were found in about 80% of coinfected patients. Bilateral pulmonary infiltrates were the most common radiographic finding in coinfected patients (51.8%), and pulmonary cavitation was the rarest event (5.4%). The mortality rate was 2.8 times higher in the TB HIV coinfected group (39.3%) than in TB patients without HIV (18.5%). Actions targeting the TB HIV-coinfected population, based on national and international recommendations, are necessary to improve prognosis and outcomes in TB and HIV infection in the institution.

  17. The induction of CD80 and apoptosis on B cells and CD40L in CD4+ T cells in response to seasonal influenza vaccination distinguishes responders versus non-responders in healthy controls and aviremic ART-treated HIV-infected individuals

    PubMed Central

    Powell, Anna M.; Luo, Zhenwu; Martin, Lisa; Wan, Zhuang; Ma, Lei; Liao, Guoyang; Song, Yuxia; Li, Xiaochun; Kilby, J. Michael; Huang, Lei; Jiang, Wei

    2016-01-01

    Background Studies have shown that HIV infection is associated with an impaired influenza vaccine response. We examined the role of cellular phenotypes and function in influenza vaccine responsiveness in healthy controls and aviremic HIV-infected subjects on antiretroviral treatment (ART). Methods 16 healthy controls and 26 ART+ aviremic HIV+ subjects were enrolled in the current study. Blood was collected at pre-vaccination (D0), and on days 7–10 (D7) and 14–21 (D14) following the 2013–2014 seasonal influenza vaccine administrations. Subjects were classified as responders if neutralizing titers against H1N1 virus increased ≥ 4-fold at D14 compared to D0. A serial analysis of B and CD4+ T cell frequencies and activation was performed on D0 and D7 by flow cytometry. Results 9 of 26 (34.6%) HIV-infected individuals and 7 of 16 (43.8%) healthy controls were classified as responders to influenza vaccines. Total B cell apoptosis (annexin V) was increased on D7 post-vaccination in non-responders but not in responders among both controls and HIV+ subjects. Surface CD80 expression on memory B cells and intracellular CD40L expression on memory CD4+ T cells were induced on D7 in responders of controls but not in non-responders. The CD80 and CD40L induction was not demonstrable in HIV-infected subjects regardless of responders and non-responders. Memory CD4+ T cell cycling tended to increase on D7 in the four study groups but did not achieve significance. All the other parameters were indistinguishable between responders and non-responders, regardless of HIV-infection status. Conclusion The perturbation of activation and apoptotic induction on B cells or CD4+ T cells after seasonal influenza vaccination in non-responders and HIV-infected subjects may help understand the mechanism of impaired vaccine responsiveness. PMID:28017428

  18. Reboxetine for ADHD in children non-responders or with poor tolerance to methylphenidate: a prospective long-term open-label study.

    PubMed

    Quintero, Javier; López-Muñoz, Francisco; Alamo, Cecilio; Loro, Mercedes; García-Campos, Natalia

    2010-11-01

    Up to 30% of patients with attention-deficit hyperactivity disorder (ADHD) treated with psychostimulants discontinue the treatment because of intolerance or lack of therapeutic response. Therapeutic alternatives are needed for such patients. In the present case series, we study the effectiveness of reboxetine over a period of 6 months in a sample of 14 children diagnosed with ADHD according to DSM-IV-TR criteria, who had responded only partially or had presented poor tolerance to conventional treatment with methylphenidate. Clinical efficacy was evaluated through the application of the 18-item Attention-Deficit Hyperactivity Disorder Rating Scale (ADHD-RS-IV) and the Clinical Global Impressions-Global Improvement Scale (CGI-I). Percentages of responders (ADHD-RS ≥ 25%) and improvers (CGI-I absolute value < 4) were 90.9 and 72.7%, respectively. No serious side-effects were observed during treatment, the most frequent effects being headaches and insomnia. The initial findings of our study show that reboxetine may constitute an effective tool for long-term treatment of children with ADHD who present poor response or poor tolerance to initial treatment with methylphenidate.

  19. Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders.

    PubMed

    D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

    2017-01-01

    Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient's preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed.

  20. Response to pegylated interferon plus ribavirin in HIV-infected patients with chronic hepatitis C due to genotype 4.

    PubMed

    Martín-Carbonero, L; Puoti, M; García-Samaniego, J; De Luca, A; Losada, E; Quinzan, G; Bruno, R; Mariño, A; González, M; Núñez, M; Soriano, V

    2008-10-01

    Hepatitis C virus (HCV) genotypes 1 and 4 respond less well to pegylated interferon (pegIFN) plus ribavirin (RBV) therapy. For this reason most studies merge these two genotypes when assessing virological response. However, in most trials the HCV genotype 4 population is rather small, and conclusions are mainly derived from what occurs in HCV-1 patients. All HCV-4 patients coinfected with HIV who received pegIFN plus RBV in two different multicentre studies, PRESCO and ROMANCE, conducted respectively in Spain and Italy, were retrospectively analyzed. Baseline plasma HCV-RNA, proportion of patients with HCV-RNA <10 IU / mL at week 4 (rapid virological response), and HCV-RNA declines >2 logs at week 12 (early virological response, EVR) were all assessed as predictors of sustained virological response (SVR). Overall, 75 patients (60 men) were evaluated. Median age was 40 years and median CD4 count 598 cells / mm(3); 49% had plasma HIV-RNA <50 copies / mL; 71% had elevated liver enzymes and 31% had advanced liver fibrosis (Metavir F3-F4). Median serum HCV-RNA was 5.7 log IU / mL. Rapid virological response was attained by 10 (20%) patients and EVR by 26 (42%). Using intention-to-treat and on-treatment (OT) analyses, SVR was achieved by 21 / 75 (28%) and 21 / 62 (34%) of HCV-4 patients, respectively. In the multivariate analysis (OT), baseline HCV-RNA (OR 0.09 for every log increment; 95% CI: 0.01-0.7) and EVR (OR: 7.08; 95% CI: 1.8-27.2) were significantly and independently associated with SVR. This is the largest series of HIV-infected patients with chronic hepatitis C due to HCV-4 treated with pegIFN plus RBV examined so far and the results show that HCV-4 behaves similarly to HCV-1. Therefore, these patients should be considered as difficult to treat population. Baseline serum HCV-RNA and EVR are the best predictors of SVR in HCV-4 / HIV-coinfected patients.

  1. Bone Mineral Density Response from Teriparatide in Patients with Osteoporosis.

    PubMed

    Kim, So-Young; Zhang, Meng; Bockman, Richard

    2017-07-01

    A review of data from large clinical trials reported more than 90% of subjects significantly improved their bone mineral density (BMD) at the lumbar spine (LS) with teriparatide (TPTD) (bone 39:1268-1275, 1). However, our clinical experience suggests that many patients may be non-responders, raising questions as to the true efficacy of TPTD in improving BMD in osteoporotic patients. The purpose of the study is to determine the rate of improvement in BMD following 18-24 months of teriparatide (TPTD) in patients with osteoporosis within an orthopedic hospital setting. This is a retrospective chart review of patients with osteoporosis who completed 18-24 months of TPTD therapy. The primary endpoint was the change in BMD at lumbar spine (LS) and hip-femoral neck (FN) and total hip (TH) following treatment. Secondary endpoints included the effect of prior bisphosphonate therapy, age, body mass index (BMI) and family history of fracture on BMD response, and the changes in bone-specific markers during active treatment. Seventy-eight women and men with mean T-scores at the LS = -2.63 met the inclusion criteria. The overall group showed a 10.7% increase in LS-BMD after 24 months of TPTD. Eighty-three percent were considered responders defined as ≥3.0% increase in LS-BMD. Non-responders (16.7%) had mean LS-BMD change = -1.41%. No difference in baseline vitamin D, calcium, creatinine, BMI, age, gender, prior fracture history, or bisphosphonate use was observed between responders and non-responders. No consistent pattern of change in measures of bone markers was noted between responders and non-responders. Eighty-three percent of patients with osteoporosis showed a >3% increase in BMD after TPTD treatment. Baseline parameters, prior bisphosphonate therapy, and the changes in bone markers showed no correlation with final BMD outcome.

  2. Carvedilol for primary prophylaxis of variceal bleeding in cirrhotic patients with haemodynamic non-response to propranolol.

    PubMed

    Reiberger, Thomas; Ulbrich, Gregor; Ferlitsch, Arnulf; Payer, Berit Anna; Schwabl, Philipp; Pinter, Matthias; Heinisch, Birgit B; Trauner, Michael; Kramer, Ludwig; Peck-Radosavljevic, Markus

    2013-11-01

    Non-selective β-blockers or endoscopic band ligation (EBL) are recommended for primary prophylaxis of variceal bleeding in patients with oesophageal varices. Additional α-adrenergic blockade (as by carvedilol) may increase the number of patients with haemodynamic response (reduction in hepatic venous pressure gradient (HVPG) of ≥ 20% or to values <12 mm Hg). Patients with oesophageal varices undergoing measurement of HVPG before and under propranolol treatment (80-160 mg/day) were included. HVPG responders were kept on propranolol (PROP group), while non-responders were placed on carvedilol (6.25-50 mg/day). Carvedilol responders continued treatment (CARV group), while non-responders to carvedilol underwent EBL. The primary aim was to assess haemodynamic response rates to carvedilol in propranolol non-responders. 36% (37/104) of patients showed a HVPG response to propranolol. Among the propranolol non-responders 56% (38/67) eventually achieved a haemodynamic response with carvedilol, while 44% (29/67) patients were finally treated with EBL. The decrease in HVPG was significantly greater with carvedilol (median 12.5 mg/day) than with propranolol (median 100 mg/day): -19 ± 10% versus -12 ± 11% (p<0.001). During a 2 year follow-up bleeding rates for PROP were 11% versus CARV 5% versus EBL 25% (p=0.0429). Fewer episodes of hepatic decompensation (PROP 38%/CARV 26% vs EBL 55%; p=0.0789) and significantly lower mortality (PROP 14%/CARV 11% vs EBL 31%; p=0.0455) were observed in haemodynamic responders compared to the EBL group. Carvedilol leads to a significantly greater decrease in HVPG than propranolol. Using carvedilol for primary prophylaxis a substantial proportion of non-responders to propranolol can achieve a haemodynamic response, which is associated with improved outcome with regard to prevention of variceal bleeding, hepatic decompensation and death.

  3. Retinopathy in chronic hepatitis C patients during interferon treatment with ribavirin

    PubMed Central

    Jain, K; Lam, W; Waheeb, S; Thai, Q; Heathcote, J

    2001-01-01

    AIM—To assess the ocular effect of interferon alfa 2b prescribed with ribavirin in patients undergoing therapy for chronic hepatitis C.
METHODS—19 patients with chronic hepatitis C who satisfied the follow up criteria were assessed for ocular complications using slit lamp biomicroscopy and indirect ophthalmoscopy before, during, and after the treatment at regular intervals.
RESULTS—8/19 patients, while on treatment, developed an asymptomatic retinopathy. Among these 3/8 were relapsers and 5/9 were non-responders to interferon monotherapy. All retinal changes faded, often while the patients continued the therapy. There was no significant association in occurrence of retinopathy with haematological and/or biochemical changes.
CONCLUSION—Retinopathy was more common in interferon monotherapy non-responders than relapsers when treated with interferon alfa 2b with the addition of ribavirin. The changes were transient, disappearing while the patients were still being treated.

 PMID:11567959

  4. Electrodermal activation in first-episode psychotic patients and their first-degree relatives.

    PubMed

    Iacono, W G; Ficken, J W; Beiser, M

    1999-10-18

    We hypothesized that electrodermal deviations evident in patients with schizophrenia would also be present in their biological relatives and examined the specificity of abnormal EDA to schizophrenia patients and their families. One hundred and thirty-five first-episode psychotic patients with either schizophrenia or other psychotic disorders; 104 non-psychiatric comparison subjects; 178 relatives of these subjects; and a comparison group of 61 patients with chronic schizophrenia had their EDA monitored while they listened to auditory stimuli. Electrodermal non-responding, regardless of the nature of the stimulus, was common to all patient groups and tended to run in families. However, non-responding did not differentiate the relatives of the psychotic patients from those of non-psychiatric subjects. Responders in both the chronic and first-episode schizophrenia patients showed an excessively high rate of non-specific fluctuations (NSFs), as did the first-degree relatives of the first-episode patients. Patients with major depression had more NSFs than normal, but significantly so only during one of the tone series. Their relatives, however, had a high NSF rate in both tone series. The results indicate that a high NSF rate may represent a psychophysiological marker of risk for schizophrenia and psychotic depression. Electrodermal non-responding is not specific to schizophrenia and is not likely to be useful as an indicator of genetic risk.

  5. Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders

    PubMed Central

    D’Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

    2017-01-01

    Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab) as well as interleukin (IL)-12/23 (ustekinumab) and IL-17 (secukinumab) inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient’s preferences (e.g., administration route), and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed. PMID:28280401

  6. Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain.

    PubMed

    Adorini, L; Harvey, M A; Miller, A; Sercarz, E E

    1979-08-01

    We have examined the ability of two purified peptide fragments derived from hen (chicken) egg-white lysozyme (HEL); N-terminal, Co-terminal peptide (a.a. 1--17:cys 6--cys 127:120--129) and mixed disulfide LII peptide (LII) (a.a. 13--105) to induce antigen-specific suppression or help in B10 (H-2b) nonresponder and B10.A (H-2a) responder mice. An anti-HEL primary in vitro antibody response can be obtained in either strain by stimulation with HEL coupled to erythrocytes (RBC). Preimmunization with HEL-complete Freund's adjuvant-(CFA) or N-C-CFA-induced suppression of the anti-HEL PFC response to HEL-RBC in spleen cell cultures from B10 mice, whereas helper activity was demonstrated in cultures from B10.A mice similarly immunized. LII-CFA priming elicited helper cells in both C57BL/10 Sn (B10) and B10.A/SgSn (B10.A) mice. The genetic nonresponsiveness of B10 mice to HEL can therefore be attributed to the activation of suppressor T cells by a limited portion of the molecule (e.g., N-C) which prevent the potential response directed against other epitopes on the same molecule (e.g., LII). One manifestation of major histocompatibility complex gene activity appears to be the intramolecular selection of different antigenic determinants leading to activation of functionally different T-cell subpopulations.

  7. Baseline Gene Expression Signatures in Monocytes from Multiple Sclerosis Patients Treated with Interferon-beta

    PubMed Central

    Bustamante, Marta F.; Nurtdinov, Ramil N.; Río, Jordi; Montalban, Xavier; Comabella, Manuel

    2013-01-01

    Background A relatively large proportion of relapsing-remitting multiple sclerosis (RRMS) patients do not respond to interferon-beta (IFNb) treatment. In previous studies with peripheral blood mononuclear cells (PBMC), we identified a subgroup of IFNb non-responders that was characterized by a baseline over-expression of type I IFN inducible genes. Additional mechanistic experiments carried out in IFNb non-responders suggested a selective alteration of the type I IFN signaling pathway in the population of blood monocytes. Here, we aimed (i) to investigate whether the type I IFN signaling pathway is up-regulated in isolated monocytes from IFNb non-responders at baseline; and (ii) to search for additional biological pathways in this cell population that may be implicated in the response to IFNb treatment. Methods Twenty RRMS patients classified according to their clinical response to IFNb treatment and 10 healthy controls were included in the study. Monocytes were purified from PBMC obtained before treatment by cell sorting and the gene expression profiling was determined with oligonucleotide microarrays. Results and discussion Purified monocytes from IFNb non-responders were characterized by an over-expression of type I IFN responsive genes, which confirms the type I IFN signature in monocytes suggested from previous studies. Other relevant signaling pathways that were up-regulated in IFNb non-responders were related with the mitochondrial function and processes such as protein synthesis and antigen presentation, and together with the type I IFN signaling pathway, may also be playing roles in the response to IFNb. PMID:23637780

  8. [Valuation of APRI and Forns models for non-invasive diagnosis of fibrosis in patients with hepatitis C in coinfected and non-coinfected with HIV].

    PubMed

    Ramos Paesa, C; Marcilla, F; López, G; Hueso, E; Pascual, A; Aguirre, J M

    2007-08-01

    APRI and Forns (IF) index are noninvasive models consisting of routine laboratory data for the prediction of liver fibrosis in patients with chronic hepatitis C. The aim of our study was to confirm the value of these models to predict significant fibrosis in these patients and if they may decrease the need for performing liver biopsy specimens in coinfected and HIVnon-coinfected. We included 60 patients with chronic hepatitis C and histologic data, 33 were coinfected with HIV. Mild fibrosis (F0-F1) was found in 73% patients, severe fibrosis (F3-F4) in 23% and cirrhosis in 18.3%. We calculated and compared APRI and IF with the stage of liver fibrosis. The APRI score < 0.5 or > 1.5 and IF < 4.2 or > 6.9, as predictors of mild or severe fibrosis, were only available in 53% and 49%. Neither laboratory nor APRI and IF were associated with liver fibrosis in non-coinfected patients. We only found association in HIV coinfected patients: severe fibrosis (F3-4) whit higher gammaglobulins [24.5% vs. 30% (p < 0.05)] and Gamma-GT levels [77 (46.5) vs. 32 (48.5) (p < 0.05)], and lower prothrombin time [72% vs. 91% (p < 0.05) ] and platelets.109 count [129 (40) vs. 170 (78) (p < 0.05)]; APRI was lower than 0.5 in 41.6% patients with mild fibrosis (F0-1) against none with severe (F3-4) (p < 0.05); specifity (E) of APRI < 0.5 for predicting mild fibrosis was 100%, but sensivity (S) was very low (41%), with a positive preditive value (VPP) of 100%, but a negative predictive value (VPN) also very low ( 36.3%). Our study showed that these models don t avoid the need for liver biopsies. More than a half of patients are not appropriately classified according to findings on liver biopsy and S and VPN are very low. The combination of these index with gammaglobulins, Gamma-GT, AST, ALT and platelet levels and protrombine time, only may be an approach to degree of fibrosis or inflammation liver in HIV co-infected patients.

  9. Impact of HIV infection on sustained virological response to treatment against hepatitis C virus with pegylated interferon plus ribavirin.

    PubMed

    Monje-Agudo, P; Castro-Iglesias, A; Rivero-Juárez, A; Martínez-Marcos, F; Ortega-González, E; Real, L M; Pernas, B; Merchante, N; Cid, P; Macías, J; Merino, M D; Rivero, A; Mena, A; Neukam, K; Pineda, J A

    2015-10-01

    It is commonly accepted that human immunodeficiency (HIV) coinfection negatively impacts on the rates of sustained virological response (SVR) to therapy with pegylated interferon plus ribavirin (PR). However, this hypothesis is derived from comparing different studies. The aim of this study was to determine the impact of HIV coinfection on SVR to PR in one single population. In a multicentric, prospective study conducted between 2000 and 2013, all previously naïve hepatitis C virus (HCV)-infected patients who started PR in five Spanish hospitals were analyzed. SVR was evaluated 24 weeks after the scheduled end of therapy. Of the 1046 patients included in this study, 413 (39%) were coinfected with HIV. Three hundred and forty-one (54%) HCV-monoinfected versus 174 (42%) HIV/HCV-coinfected patients achieved SVR (p < 0.001). The corresponding figures for undetectable HCV RNA at treatment week 4 were 86/181 (47%) versus 59/197 (30%), p < 0.001. SVR was observed in 149 (69%) HCV genotype 2/3-monoinfected subjects versus 91 (68%) HIV/HCV genotype 2/3-coinfected subjects (p = 0.785). In the HCV genotype 1/4-infected population, 188 (46%) monoinfected patients versus 82 (30%) with HIV coinfection (p < 0.001) achieved SVR. In this subgroup, absence of HIV coinfection was independently associated with higher SVR [adjusted odds ratio (95% confidence interval): 2.127 (1.135-3.988); p = 0.019] in a multivariate analysis adjusted for age, sex, baseline HCV RNA load, IL28B genotype, fibrosis stage, and type of pegylated interferon. HIV coinfection impacts on the rates of SVR to PR only in HCV genotype 1/4-infected patients, while it has no effect on SVR in the HCV genotype 2/3-infected subpopulation.

  10. High rates of hepatitis C virus (HCV) cure using direct-acting antivirals in HIV/HCV-coinfected patients: a real-world perspective.

    PubMed

    Hawkins, Claudia; Grant, Jennifer; Ammerman, Lauren Rose; Palella, Frank; Mclaughlin, Milena; Green, Richard; Mcgregor, Donna; Stosor, Valentina

    2016-09-01

    There are few data on the real-world experience of FDA-approved oral hepatitis C virus (HCV) direct-acting antiviral (DAA) drug combinations in HIV/HCV-coinfected patients. We evaluated the safety and efficacy of DAA therapies in a cohort of HIV/HCV patients in a large urban clinic in Chicago. HIV/HCV-coinfected adults (≥18 years) enrolled in the Northwestern University Viral Hepatitis Registry between January 2013 and June 2015 were analysed. Treated patients received one of the following DAA combinations: sofosbuvir/ledipasvir, sofosbuvir/ribavirin, sofosbuvir/simeprevir or paritaprevir/ritonavir/ombitasvir/dasabuvir ± ribavirin. The primary outcome was sustained virological response at 12 weeks after DAA completion (SVR12). Seventy-seven HIV/HCV patients were evaluated for DAA therapy. Most patients were male (62/77, 81%) and infected with HCV genotype 1 (67/77, 87%). Some 32/77 (42%) were cirrhotic and 29/77 (38%) had received prior treatment with an IFN-containing regimen. DAA therapy was more likely to be started in Caucasians than persons of other ethnicities (P = 0.01). The overall SVR12 rate was 92% in 52 patients who completed therapy and had follow-up by the end of the study: sofosbuvir/simeprevir, 32/33 (97%); sofosbuvir/ribavirin, 4/7 (57%); sofosbuvir/ledipasvir, 11/11 (100%); and paritaprevir/ritonavir/ombitasvir/dasabuvir, 1/1 (100%). Four patients relapsed after therapy with sofosbuvir/simeprevir (n = 1) or sofosbuvir/ribavirin (n = 3). Adverse events were uncommon and did not result in DAA treatment interruption or discontinuation. The HCV DAA combinations of sofosbuvir/ledipasvir and sofosbuvir/simeprevir were highly effective and well tolerated in this diverse population of HIV/HCV-coinfected patients, many of whom had advanced liver disease. HIV coinfection should not be considered a barrier to successful HCV treatment with DAAs. © The Author 2016. Published by Oxford University Press on behalf of the British Society for

  11. High Cure Rate With 24 Weeks of Daclatasvir-Based Quadruple Therapy in Treatment-Experienced, Null-Responder Patients With HIV/Hepatitis C Virus Genotype 1/4 Coinfection: The ANRS HC30 QUADRIH Study.

    PubMed

    Piroth, Lionel; Paniez, Hubert; Taburet, Anne Marie; Vincent, Corine; Rosenthal, Eric; Lacombe, Karine; Billaud, Eric; Rey, David; Zucman, David; Bailly, François; Bronowicki, Jean-Pierre; Simony, Mélanie; Diallo, Alpha; Izopet, Jacques; Aboulker, Jean-Pierre; Meyer, Laurence; Molina, Jean-Michel

    2015-09-01

    Few direct anti-hepatitis C virus (HCV) agents have been studied in difficult-to-treat null responder and cirrhotic human immunodeficiency virus (HIV)-coinfected patients. Daclatasvir and asunaprevir combined with pegylated interferon/ribavirin (peg-IFN/RBV) have shown promising results in HCV-monoinfected patients. An open-label, single-arm, phase 2 study was conducted in HIV/HCV genotype 1/4-coinfected patients who were null responders to prior peg-IFN/RBV standard therapy and on a raltegravir-based regimen with HIV RNA <400 copies/mL. They received a 4-week lead-in phase with peg-IFN/RBV, followed by 24 weeks of asunaprevir (100 mg twice daily), daclatasvir (60 mg once daily), and peg-IFN/RBV. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12) using intent-to-treat analysis. Seventy-five patients were included, of whom 27 (36%) had cirrhosis. The median baseline CD4 count was 748 (interquartile range, 481-930) cells/µL. The global SVR12 rate was 96.0% (95% confidence interval [CI], 88.8%-99.2%; n = 72/75), 92.6% (95% CI, 75.7%-99.1%; n = 25/27) in cirrhotic patients, 94.6% (95% CI, 81.8%-99.3%; n = 35/37) in genotype 1 patients, and 97.4% (95% CI, 86.2%-99.9%; n = 37/38) in genotype 4 patients. Six patients (8%) stopped HCV therapy prematurely: 2 due to HCV breakthrough, 4 to adverse events (1 lung cancer, 3 infections). One patient with cirrhosis (with baseline platelet count <150 000 platelets/µL and albuminemia <35 g/L) died from multiorgan failure. Overall, 36 serious adverse events occurred in 21 (28%) patients. No HIV breakthrough was observed. In HIV/HCV genotype 1/4-coinfected null responders, a 24-week regimen combining daclatasvir, asunaprevir, and peg-IFN/RBV was associated with a very high cure rate. The safety profile was acceptable, even though cirrhotic patients with low albuminemia and platelets should be monitored closely. This combination is a new option in this difficult-to-treat population. NCT

  12. Antecedent life events, social supports and response to antidepressants in depressed patients.

    PubMed

    Tomaszewska, W; Peselow, E D; Barouche, F; Fieve, R R

    1996-11-01

    We evaluated 355 subjects who entered one of six double-blind placebo-controlled antidepressant drug trials with respect to the occurrence of antecedent adverse life events and their meaning to the patient. Patients were also assessed with regard to the degree of social support they received for the negative life event. The groups differed as to whether they did or did not meet the criteria for melancholic depression; 43 one-week placebo responders were statistically significantly more likely to believe that adverse life events predisposed them to depressive illness and that such life events precipitated their current depression, compared to 312 one-week placebo non-responders. Of the 312 patients who went on to the double-blind phase in which they were treated with either drug (n = 204) or placebo (n = 108), it was noted that, for both melancholic and non-melancholic patients, responders to drug treatment (but not placebo) had a more favourable ratio of social support received/social support desired than non-responders. Non-melancholic responders to both drug and placebo were statistically significantly more likely to report fewer adverse life events and have a less strong belief that adverse life events predispose one to depressive illness than non-responders. Melancholic patients did not show this trend.

  13. Potential determinants of efficacy of mirror therapy in stroke patients – A pilot study

    PubMed Central

    Brunetti, Maddalena; Morkisch, Nadine; Fritzsch, Claire; Mehnert, Jan; Steinbrink, Jens; Niedeggen, Michael; Dohle, Christian

    2015-01-01

    Abstract Background: Mirror therapy (MT) was found to improve motor function after stroke. However, there is high variability between patients regarding motor recovery. Objectives: The following pilot study was designed to identify potential factors determining this variability between patients with severe upper limb paresis, receiving MT. Methods: Eleven sub-acute stroke patients with severe upper limb paresis participated, receiving in-patient rehabilitation. After a set of pre-assessments (including measurement of brain activity at the primary motor cortex and precuneus during the mirror illusion, using near-infrared spectroscopy as described previously), four weeks of MT were applied, followed by a set of post-assessments. Discriminant group analysis for MT responders and non-responders was performed. Results: Six out of eleven patients were defined as responders and five as non-responders on the basis of their functional motor improvement. The initial motor function and the activity shift in both precunei (mirror index) were found to discriminate significantly between responders and non-responders. Conclusions: In line with earlier results, initial motor function was confirmed as crucial determinant of motor recovery. Additionally, activity response to the mirror illusion in both precunei was found to be a candidate for determination of the efficacy of MT. PMID:26409402

  14. Potential determinants of efficacy of mirror therapy in stroke patients--A pilot study.

    PubMed

    Brunetti, Maddalena; Morkisch, Nadine; Fritzsch, Claire; Mehnert, Jan; Steinbrink, Jens; Niedeggen, Michael; Dohle, Christian

    2015-01-01

    Mirror therapy (MT) was found to improve motor function after stroke. However, there is high variability between patients regarding motor recovery. The following pilot study was designed to identify potential factors determining this variability between patients with severe upper limb paresis, receiving MT. Eleven sub-acute stroke patients with severe upper limb paresis participated, receiving in-patient rehabilitation. After a set of pre-assessments (including measurement of brain activity at the primary motor cortex and precuneus during the mirror illusion, using near-infrared spectroscopy as described previously), four weeks of MT were applied, followed by a set of post-assessments. Discriminant group analysis for MT responders and non-responders was performed. Six out of eleven patients were defined as responders and five as non-responders on the basis of their functional motor improvement. The initial motor function and the activity shift in both precunei (mirror index) were found to discriminate significantly between responders and non-responders. In line with earlier results, initial motor function was confirmed as crucial determinant of motor recovery. Additionally, activity response to the mirror illusion in both precunei was found to be a candidate for determination of the efficacy of MT.

  15. Long-term survival of patients with critical limb ischemia treated with iloprost: response rate and predictive criteria. A retrospective analysis of 102 patients.

    PubMed

    Melillo, E; Lucaccini, E; Berchiolli, R; Adami, D; Nuti, M; Dell'Omo, G; Farina, A; Panigada, G; Roberts, A T; Meini, S

    2016-12-01

    Critical limb ischemia (CLI) patients have poor long-term prognosis. We showed that iloprost improves outcomes (major amputation and survival) up a 5-year follow-up, but it is not known if in this length of time the survival curves, of clinical responders and non-responders, differ. A retrospective study enrolling 102 consecutive patients between 2004-2008, with clinical and instrumental (ultrasound, angiography, transcutaneous tensiometry of oxygen TcpO2 and carbon dioxide TcpCO2 in the affected and contralateral limbs) diagnosis of critical ischemia. All patients received the best medical therapy. Iloprost was administered (0.5-2 ng/kg/min 6 hours/day for 2-4 weeks) in all patients initially considered unsuitable for revascularization, repeating it regularly in time every six-twelve months in the case of positive response. The minimum expected follow-up was 4 years. 71.5% of patients were treated with iloprost and the responder rate was 71.2%. Most of the patients were regularly retreated with repeated cycles. Initial median supine TcpCO2 in symptomatic limb was higher in untreated patients than those treated (58 vs. 49 mmHg; p < 0.05) and in non-responders compared to responders (60 vs. 49 mmHg; p < 0.05). TcpCO2 directly and significantly correlated with the highest risk of mortality and seems to represent a new accurate prognostic criterion of unfavourable short and long-term response to prostanoid. In iloprost group, major amputations were significantly reduced. Revascularization was significantly higher in non-responders (57.1% vs. 11.5%; p < 0.05). There was a significantly higher prevalence of subsequent myocardial infarction in the non-iloprost group (27.6% vs. 9.6%; p < 0.05). The survival rate of non-responders was higher than untreated up until the second year (76.2% vs. 62%; p < 0.05). At 4 years we found higher survival in patients treated with iloprost (64.3% vs. 41% in untreated; p < 0.05) and in responders (75% vs. 38.1% in non-responders; p < 0

  16. Genetic Polymorphism of CYP2D6 and Clomiphene Concentrations in Infertile Patients with Ovulatory Dysfunction Treated with Clomiphene Citrate.

    PubMed

    Ji, Misuk; Kim, Kwang-Rae; Lee, Woochang; Choe, Wonho; Chun, Sail; Min, Won-Ki

    2016-02-01

    CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations.

  17. Factors associated with the glucose-lowering effect of vildagliptin identified from the results of the oral glucose tolerance test in Japanese patients with type 2 diabetes.

    PubMed

    Nakamura, Akinobu; Terauchi, Yasuo

    2013-01-01

    In order to investigate the factors contributing to the glucose-lowering effect of vildagliptin, we analyzed the results of the oral glucose tolerance test together with several clinical parameters in Japanese patients with type 2 diabetes before and after 24 weeks of treatment with vildagliptin. The data of the 13 patients who satisfactorily completed the follow-up examinations were included. After 24 weeks treatment with vildagliptin, the patients were classified into a responder group (69.2%) and a non-responder group (30.8%); the responders consisting of subjects whose HbA1c decreased following 24 weeks treatment with vildagliptin, and the non-responders consisting of subjects who did not show any significant decrease of HbA1c. There were no differences in baseline characteristics between the two groups before administration of vildagliptin. After 24 weeks of treatment, HbA1c was significantly reduced from 7.3 ± 0.5% to 6.7 ± 0.5% in the responder group (P = 0.0077), while it tended to rather increased from 7.1 ± 0.6% to 7.5 ± 0.7% in the non-responder group (P = 0.0679). Also, parameters reflecting the glucose-stimulated insulin secretion, such as the insulinogenic index and oral disposition index, were significantly higher in the responder group than in the non-responder group, whereas insulin sensitivity was similar between the two groups. These results suggest that the difference in the degree of improvement of the glucose tolerance between the responder group and non-responder group in this study could be associated with the effect of vildagliptin on the glucose-stimulated insulin secretion, but not on the insulin sensitivity.

  18. Identification of genetic markers for treatment success in heart failure patients: insight from cardiac resynchronization therapy.

    PubMed

    Schmitz, Boris; De Maria, Renata; Gatsios, Dimitris; Chrysanthakopoulou, Theodora; Landolina, Maurizio; Gasparini, Maurizio; Campolo, Jonica; Parolini, Marina; Sanzo, Antonio; Galimberti, Paola; Bianchi, Michele; Lenders, Malte; Brand, Eva; Parodi, Oberdan; Lunati, Maurizio; Brand, Stefan-Martin

    2014-12-01

    Cardiac resynchronization therapy (CRT) can improve ventricular size, shape, and mass and reduce mitral regurgitation by reverse remodeling of the failing ventricle. About 30% of patients do not respond to this therapy for unknown reasons. In this study, we aimed at the identification and classification of CRT responder by the use of genetic variants and clinical parameters. Of 1421 CRT patients, 207 subjects were consecutively selected, and CRT responder and nonresponder were matched for their baseline parameters before CRT. Treatment success of CRT was defined as a decrease in left ventricular end-systolic volume >15% at follow-up echocardiography compared with left ventricular end-systolic volume at baseline. All other changes classified the patient as CRT nonresponder. A genetic association study was performed, which identified 4 genetic variants to be associated with the CRT responder phenotype at the allelic (P<0.035) and genotypic (P<0.031) level: rs3766031 (ATPIB1), rs5443 (GNB3), rs5522 (NR3C2), and rs7325635 (TNFSF11). Machine learning algorithms were used for the classification of CRT patients into responder and nonresponder status, including combinations of the identified genetic variants and clinical parameters. We demonstrated that rule induction algorithms can successfully be applied for the classification of heart failure patients in CRT responder and nonresponder status using clinical and genetic parameters. Our analysis included information on alleles and genotypes of 4 genetic loci, rs3766031 (ATPIB1), rs5443 (GNB3), rs5522 (NR3C2), and rs7325635 (TNFSF11), pathophysiologically associated with remodeling of the failing ventricle. © 2014 American Heart Association, Inc.

  19. Determinants of Pain Treatment Response and Non-Response: Identification of TMD Patient Subgroups

    PubMed Central

    Litt, Mark D.; Porto, Felipe B.

    2013-01-01

    The purpose of the present study was to determine if we could identify a specific subtype of temporomandibular disorder (TMD) pain patients that does not respond to treatment. Patients were 101 men and women with chronic TMD pain recruited from the community and randomly assigned to one of two treatment conditions: a standard conservative care (STD) condition or a standard care plus cognitive-behavioral treatment condition (STD+CBT) in which patients received all elements of STD, but also received cognitive-behavioral coping skills training. Growth mixture modeling, incorporating a series of treatment-related predictors, was used to distinguish several distinct classes of responders or non-responders to treatment based on reported pain over a one-year follow-up period. Results indicated that treatment non-responders accounted for 16% of the sample, and did not differ from treatment responders on demographics or temporomandibular joint pathology, but that they reported more psychiatric symptoms, poorer coping, and higher levels of catastrophizing. Treatment-related predictors of membership in treatment responder groups versus the non-responder group included the addition of CBT to standard treatment, treatment attendance, and decreasing catastrophization. It was concluded that CBT may be made more efficacious for TMD patients by placing further emphasis on decreasing catastrophization and on individualizing care. PMID:24094979

  20. Relationship between the clinical efficacy and AUC/MIC of intravenous ciprofloxacin in Japanese patients with intraabdominal infections.

    PubMed

    Ohki, Emiko; Yamagishi, Yuka; Mikamo, Hiroshige

    2013-10-01

    The efficacy of fluoroquinolones (FQs) correlates with the pharmacokinetic/pharmacodynamic (PK-PD) parameter, AUC/MIC. To our knowledge, however, no prospective studies have reported the relationship between FQ efficacy and PK-PD parameters in intraabdominal infection; therefore, we prospectively investigated the relationship between the efficacy of intravenous ciprofloxacin (CPFX IV) and PK-PD parameters. The study included 16 patients diagnosed with peritonitis between 2006 and 2008: 14 patients infected with a single organism and 2 patients infected with more than one organism. Each patient was treated with CPFX IV (300 mg twice daily). The response rate was 56% (9 responders and 7 non-responders). Non-responders were infected with Escherichia coli, Pseudomonas aeruginosa, and Bacteroides fragilis (6 patients were infected with a single organism and 1 with more than one organism). Plasma drug concentrations were measured 1 h and 2 or 4 h after administration of CPFX IV. AUC for 24 h (AUC(0-24))/MIC values was calculated. The range of AUC(0-24)/MIC values in responders [95.3-3628.4 (geometric mean, 521.6)] was significantly different from that in non-responders [7.0-45.2 (geometric mean, 16.5)] (p = 0.001). The target AUC/MIC value of CPFX IV would be considered to be 45-95 in patients with peritonitis.

  1. Evaluation of a pharmaceutical risk-sharing agreement when patients are screened for the probability of success.

    PubMed

    Mahjoub, Reza; Ødegaard, Fredrik; Zaric, Gregory S

    2017-06-19

    We analyze a game-theoretic model of a risk-sharing agreement between a payer and a pharmaceutical firm. The drug manufacturer chooses the price while the payer sets the rebate rate and decides which patients are eligible for treatment. The manufacturer provides the payer with a rebate for nonresponding patients. We generalize on the existing literature, by making both price and rebate rate decision variables, allowing the rebate rate to be different from 100%, and incorporating 2 types of administrative costs. We identify a threshold for the expected probability of response for classifying the drug as a mass-market or niche type and investigate the optimal solutions for both types. We also identify a threshold for the rebate rate at which the net benefits become equal for responding and nonresponding patients. Through numerical examples, we examine how various parameters impact the drug manufacturer's and the payer's optimal solution. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthritis patients

    PubMed Central

    Lindberg, Johan; af Klint, Erik; Catrina, Anca Irinel; Nilsson, Peter; Klareskog, Lars; Ulfgren, Ann-Kristin; Lundeberg, Joakim

    2006-01-01

    We examined the gene expression profiles in arthroscopic biopsies retrieved from 10 rheumatoid arthritis patients before and after anti-TNF treatment with infliximab to investigate whether such profiles can be used to predict responses to the therapy, and to study effects of the therapy on the profiles. Responses to treatment were assessed using European League Against Rheumatism response criteria. Three patients were found to be good responders, five patients to be moderate responders and two patients to be nonresponders. The TNF-α status of the biopsies from each of the patients before treatment was also investigated immunohistochemically, and it was detected in biopsies from four of the patients, including all three of the good responders. The gene expression data demonstrate that all patients had unique gene expression signatures, with low intrapatient variability between biopsies. The data also revealed significant differences between the good responding and nonresponding patients (279 differentially expressed genes were detected, with a false discovery rate < 0.025). Among the identified genes we found that MMP-3 was significantly upregulated in good responders (log2 fold change, 2.95) compared with nonresponders, providing further support for the potential of MMP-3 as a marker for good responses to therapy. An even more extensive list of 685 significantly differentially expressed genes was found between patients in whom TNF-α was found and nonresponders, indicating that TNF-α could be an important biomarker for successful infliximab treatment. Significant differences were also observed between biopsies taken before and after anti-TNF treatment, including 115 differentially expressed genes in the good responding group. Interestingly, the effect was even stronger in the group in which TNF-α was immunohistochemically detected before therapy. Here, 1,058 genes were differentially expressed, including many that were novel in this context (for example, CXCL3

  3. Cost-Effectiveness of Genotype 1 Chronic Hepatitis C Virus Treatments in Patients Coinfected with Human Immunodeficiency Virus in the United States.

    PubMed

    Saab, Sammy; Virabhak, Suchin; Parisé, Hélène; Johnson, Scott; Wang, Alice; Misurski, Derek; Gonzalez, Yuri Sanchez; Juday, Timothy

    2016-08-01

    New treatments for chronic hepatitis C virus (HCV) are highly effective in patients coinfected with human immunodeficiency virus (HIV). This study estimated the cost-effectiveness of treatments for genotype 1 (GT1) HCV in HIV-coinfected patients. A Markov model based on HCV natural history was used. The base-case analysis included both treatment-naïve and -experienced patients. Alternatives were ombitasvir/paritaprevir/ritonavir, dasabuvir with or without ribavirin (3D ± R) for 12 or 24 weeks, sofosbuvir plus peginterferon and R (SOF + PR) for 12 weeks, SOF + R for 24 weeks, and no treatment (NT). A subgroup analysis restricted to treatment-naïve, non-cirrhotic patients compared 3D ± R for 12 weeks to SOF plus ledipasvir (LDV) for 12 weeks and NT. Transition probabilities, utilities, and costs were obtained from the published literature. Outcomes were measured over a lifetime horizon and included rates of compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma and liver-related death, total costs, life-years, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). In the base-case, SOF + R was dominated by both SOF + PR and 3D ± R. Compared to SOF + PR, 3D ± R had an ICER of $45,581. The lifetime rates of liver morbidity and mortality were lower among those treated with 3D ± R compared to SOF + PR, SOF + R, or NT. In the subgroup analysis, 3D ± R was cost-effective compared to NT at a threshold of $50,000 per QALY (ICER $27,496). SOF/LDV had an ICER of $104,489 per QALY gained compared to 3D ± R. In the GT1 HCV population coinfected with HIV, 3D ± R was cost-effective compared to NT, SOF + R, and SOF + PR. In the treatment-naïve sub-population, 3D ± R was cost-effective compared to NT and SOF/LDV.

  4. Systemic Chemokine Levels with "Gut-Specific" Vedolizumab in Patients with Inflammatory Bowel Disease-A Pilot Study.

    PubMed

    Zwicker, Stephanie; Lira-Junior, Ronaldo; Höög, Charlotte; Almer, Sven; Boström, Elisabeth A

    2017-08-22

    Vedolizumab, a gut-specific biological treatment for inflammatory bowel disease (IBD), is an antibody that binds to the α₄β₇ integrin and blocks T-cell migration into intestinal mucosa. We aimed to investigate chemokine levels in serum of IBD-patients treated with vedolizumab. In this pilot study, we included 11 IBD patients (8 Crohn's disease, 3 ulcerative colitis) previously non-respondent to anti-tumor necrosis factor (TNF)-agents. Patients received vedolizumab at week 0, 2 and 6 and were evaluated for clinical efficacy at week 10. Clinical characteristics and routine laboratory parameters were obtained and patients were classified as responders or non-responders. Expression of 21 chemokines in serum was measured using Proximity Extension Assay and related to clinical outcome. At week 10, 6 out of 11 patients had clinically responded. Overall expression of CCL13 increased after treatment. In non-responders, expression of CCL13 and CXCL8 increased after treatment, and CCL20 and CXCL1 expressions were higher compared to responders. In responders, CCL28 decreased after treatment. C-reactive protein (CRP) correlated negatively with 6 chemokines before therapy, but not after therapy. Systemic CCL13 expression increases in IBD-patients after vedolizumab therapy and several chemokine levels differ between responders and non-responders. An increased CCL13-level when starting vedolizumab treatment, might indicate potential prognostic value of measuring chemokine levels when starting therapy with vedolizumab. This study provides new information on modulation of systemic chemokine levels after vedolizumab treatment.

  5. Systemic Chemokine Levels with “Gut-Specific” Vedolizumab in Patients with Inflammatory Bowel Disease—A Pilot Study

    PubMed Central

    Zwicker, Stephanie; Lira-Junior, Ronaldo; Höög, Charlotte

    2017-01-01

    Vedolizumab, a gut-specific biological treatment for inflammatory bowel disease (IBD), is an antibody that binds to the α4β7 integrin and blocks T-cell migration into intestinal mucosa. We aimed to investigate chemokine levels in serum of IBD-patients treated with vedolizumab. In this pilot study, we included 11 IBD patients (8 Crohn’s disease, 3 ulcerative colitis) previously non-respondent to anti-tumor necrosis factor (TNF)-agents. Patients received vedolizumab at week 0, 2 and 6 and were evaluated for clinical efficacy at week 10. Clinical characteristics and routine laboratory parameters were obtained and patients were classified as responders or non-responders. Expression of 21 chemokines in serum was measured using Proximity Extension Assay and related to clinical outcome. At week 10, 6 out of 11 patients had clinically responded. Overall expression of CCL13 increased after treatment. In non-responders, expression of CCL13 and CXCL8 increased after treatment, and CCL20 and CXCL1 expressions were higher compared to responders. In responders, CCL28 decreased after treatment. C-reactive protein (CRP) correlated negatively with 6 chemokines before therapy, but not after therapy. Systemic CCL13 expression increases in IBD-patients after vedolizumab therapy and several chemokine levels differ between responders and non-responders. An increased CCL13-level when starting vedolizumab treatment, might indicate potential prognostic value of measuring chemokine levels when starting therapy with vedolizumab. This study provides new information on modulation of systemic chemokine levels after vedolizumab treatment. PMID:28829369

  6. Biochemical Response to Ursodeoxycholic Acid Predicts Survival in a North American Cohort of Primary Biliary Cirrhosis Patients

    PubMed Central

    Lammert, Craig; Juran, Brian D.; Schlicht, Erik; Chan, Landon L.; Atkinson, Elizabeth J.; de Andrade, Mariza; Lazaridis, Konstantinos N.

    2014-01-01

    Background Biochemical response to Ursodeoxycholic Acid among patients with Primary Biliary Cirrhosis remains variable and there is no agreement of an ideal model. Novel assessment of response coupled to histologic progression was recently defined by the Toronto criteria. We retrospectively assessed transplant-free survival and clinical outcomes associated with Ursodeoxycholic Acid response to evaluate the Toronto criteria using a large North American cohort of PBC patients. Methods 398 PBC patients from the Mayo Clinic PBC Genetic Epidemiology (MCPGE) Registry were assessed for Ursodeoxycholic Acid treatment and biochemical response per the Toronto criteria. Responders were defined by reduction in alkaline phosphatase to less than or equal to 1.67 times the upper normal limit by 2 years of treatment, whereas non-responders had alkaline phosphatase values greater than 1.67 times the upper normal limit. Probability of survival was estimated using the Kaplan-Meier method. Results 302 (76%) patients were responders and 96 (24%) were non-responders. Significantly more non-responders developed adverse events related to chronic liver disease compared to responders (Hazard Ratio (HR): 2.77, P = 0.001). Biochemical responders and early-stage disease at treatment start was associated with improved overall transplant-free survival compared to non-responders (HR: 1.9) and patients with late stage disease (HR: 2.7) after age and sex adjustment. Conclusions The Toronto criteria are capable of identifying Ursodeoxycholic Acid-treated Primary Biliary Cirrhosis patients at risk of poor transplant-free survival and adverse clinical outcomes. Our data reveal that despite advanced disease at diagnosis, biochemical response per the Toronto criteria associates with improved overall transplant-free survival. PMID:24317935

  7. Gene mutation analysis in EGFR wild type NSCLC responsive to erlotinib: are there features to guide patient selection?

    PubMed

    Ulivi, Paola; Delmonte, Angelo; Chiadini, Elisa; Calistri, Daniele; Papi, Maximilian; Mariotti, Marita; Verlicchi, Alberto; Ragazzini, Angela; Capelli, Laura; Gamboni, Alessandro; Puccetti, Maurizio; Dubini, Alessandra; Burgio, Marco Angelo; Casanova, Claudia; Crinò, Lucio; Amadori, Dino; Dazzi, Claudio

    2014-12-31

    Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity.

  8. Occult hepatitis B virus infection and S gene escape mutants in HIV-infected patients after hepatitis B virus vaccination.

    PubMed

    Aghakhani, Arezoo; Mohraz, Minoo; Aghasadeghi, Mohammad Reza; Banifazl, Mohammad; Vahabpour, Rouhollah; Karami, Afsaneh; Foroughi, Maryam; Ramezani, Amitis

    2016-10-01

    Hepatitis B virus (HBV) vaccination is recommended for HIV patients. Despite the relative success of HBV vaccination, breakthrough infections can occur infrequently in patients, and it can be due to occult HBV infection, vaccine unresponsiveness and/or emergence of escape mutants. This study assessed the presence of occult HBV infection and S gene escape mutants in HIV-positive patients after HBV vaccination. Ninety-two HIV-positive patients were enrolled in this study, including 52 responders to HBV vaccine and 40 non-responders. All of the cases received HBV vaccine according to routine HBV vaccination protocols. The presence of HBV-DNA was determined by real-time polymerase chain reaction (PCR). In HBV-DNA positive samples, the most conserved regions of S gene sequences were amplified by nested PCR and PCR products were sequenced. Occult HBV infection was detected in two cases. Glycine to arginine mutation at residue 145 (G145R) within the 'a' region of the S gene was detected in one of the occult HBV infection cases who was in the non-responder group. This study showed that the prevalence of occult HBV infection and vaccine escape mutants was low in our HBV-vaccinated HIV-positive patients in both responder and non-responder groups, so there was no alarming evidence indicating breakthrough HBV infection in our vaccinated HIV-positive cases. © The Author(s) 2016.

  9. Gene Mutation Analysis in EGFR Wild Type NSCLC Responsive to Erlotinib: Are There Features to Guide Patient Selection?

    PubMed Central

    Ulivi, Paola; Delmonte, Angelo; Chiadini, Elisa; Calistri, Daniele; Papi, Maximilian; Mariotti, Marita; Verlicchi, Alberto; Ragazzini, Angela; Capelli, Laura; Gamboni, Alessandro; Puccetti, Maurizio; Dubini, Alessandra; Burgio, Marco Angelo; Casanova, Claudia; Crinò, Lucio; Amadori, Dino; Dazzi, Claudio

    2014-01-01

    Tyrosine kinase inhibitors (TKIs) are very efficacious in non-small-cell lung cancer (NSCLC) patients harboring activating Epidermal Growth Factor Receptor (EGFR) mutations. However, about 10% of EGFR wild type (wt) patients respond to TKI, with unknown molecular mechanisms of sensitivity. We considered a case series of 34 EGFR wt NSCLC patients responsive to erlotinib after at least one line of therapy. Responsive patients were matched with an equal number of non-responsive EGFR wt patients. A panel of 26 genes, for a total of 214 somatic mutations, was analyzed by MassARRAY® System (Sequenom, San Diego, CA, USA). A 15% KRAS mutation was observed in both groups, with a prevalence of G12C in non-responders (80% vs. 40% in responders). NOTCH1, p53 and EGFR-resistance-related mutations were found more frequently in non-responders, whereas EGFR-sensitizing mutations and alterations in genes involved in proliferation pathways were more frequent in responders. In conclusion, our findings indicate that p53, NOTCH1 and exon 20 EGFR mutations seem to be related to TKI resistance. KRAS mutations do not appear to influence the TKI response, although G12C mutation is more frequent in non-responders. Finally, the use of highly sensitive methodologies could lead to the identification of under-represented EGFR mutations potentially associated with TKI sensitivity. PMID:25561229

  10. Does the Degree of Hepatocellular Carcinoma Tumor Necrosis following Transarterial Chemoembolization Impact Patient Survival?

    PubMed Central

    Haywood, Nathan; Gennaro, Kyle; Obert, John; Sauer, Paul F.; Redden, David T.; Zarzour, Jessica; Smith, J. Kevin; Bolus, David; Saddekni, Souheil; Aal, Ahmed Kamel Abdel; Gray, Stephen; White, Jared; Eckhoff, Devin E.; DuBay, Derek A.

    2016-01-01

    Purpose. The association between transarterial chemoembolization- (TACE-) induced HCC tumor necrosis measured by the modified Response Evaluation Criteria In Solid Tumors (mRECIST) and patient survival is poorly defined. We hypothesize that survival will be superior in HCC patients with increased TACE-induced tumor necrosis. Materials and Methods. TACE interventions were retrospectively reviewed. Tumor response was quantified via dichotomized (responders and nonresponders) and the four defined mRECIST categories. Results. Median survival following TACE was significantly greater in responders compared to nonresponders (20.8 months versus 14.9 months, p = 0.011). Survival outcomes also significantly varied among the four mRECIST categories (p = 0.0003): complete, 21.4 months; partial, 20.8; stable, 16.8; and progressive, 7.73. Only progressive disease demonstrated significantly worse survival when compared to complete response. Multivariable analysis showed that progressive disease, increasing total tumor diameter, and non-Child-Pugh class A were independent predictors of post-TACE mortality. Conclusions. Both dichotomized (responders and nonresponders) and the four defined mRECIST responses to TACE in patients with HCC were predictive of survival. The main driver of the survival analysis was poor survival in the progressive disease group. Surprisingly, there was small nonsignificant survival benefit between complete, partial, and stable disease groups. These findings may inform HCC treatment decisions following first TACE. PMID:26949394

  11. A History of Childhood Trauma and Response to Treatment With Antipsychotics in First-Episode Schizophrenia Patients: Preliminary Results.

    PubMed

    Misiak, Błażej; Frydecka, Dorota

    2016-10-01

    In this study, we aimed to investigate whether a history of childhood trauma (CT) can help predict early response to antipsychotic treatment in patients with first-episode schizophrenia (FES). We recruited 64 FES patients who were followed up after 12 weeks of treatment with second-generation antipsychotics. Symptomatic manifestation was examined using the Positive and Negative Syndrome Scale (PANSS). Childhood adversities were assessed using the Early Trauma Inventory Self-Report-Short Form. Nonresponders had significantly higher general trauma score, emotional abuse score, total trauma score, and baseline PANSS negative factor score. A history of CT was significantly more frequent among nonresponders. Logistic regression analysis revealed that positive history of CT, higher emotional abuse score, and higher baseline PANSS negative factor score are significant predictors of poor response to treatment. Our results indicate that a history of CT, especially emotional abuse, and higher severity of negative symptoms are independent predictors of poor response to treatment with antipsychotics.

  12. Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms.

    PubMed

    Medici, Bjarke Borregaard; la Cour, Jeppe Lerche; Michaelsson, Luba Freja; Faber, Jens Oscar; Nygaard, Birte

    2017-04-01

    Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). Combination therapy and the appropriate choice of blood tests to monitor treatment are highly debated among specialists and patients. To evaluate whether measuring serum triiodothyronine (S-T3) at baseline or during combination therapy can be used as an indicator of a positive effect from L-T4/L-T3 combination therapy. Observational retrospective study of patients (n = 42) with persisting symptoms of hypothyroidism despite L-T4 therapy who had normal TSH levels and did not have any comorbidities that could explain their symptoms. All were then treated with L-T4/L-T3 combination therapy at a dose ratio of 17/1 according to European Thyroid Association guidelines. Based on patient-reported outcome, they were divided into responders and nonresponders. Five patients were lost to follow-up and thus excluded. At the 3-month follow-up, 11 were classified as nonresponders and 26 as responders. At 12 months these figures had changed to 13 (35%) and 24 (65%), respectively. When comparing responders versus nonresponders, no differences were seen at baseline or during follow-up in S-T3 and in free T3 estimates. Further, logistic regression showed no correlation between S-T3 and free T3 estimates and responder/nonresponder status. Our data indicate that serum T3 measurements are not suitable to predict which patient will benefit from L-T4/L-T3 combination therapy, and treatment response cannot be followed by repeated T3 measurements either.

  13. Neither Baseline nor Changes in Serum Triiodothyronine during Levothyroxine/Liothyronine Combination Therapy Predict a Positive Response to This Treatment Modality in Hypothyroid Patients with Persistent Symptoms

    PubMed Central

    Medici, Bjarke Borregaard; la Cour, Jeppe Lerche; Michaelsson, Luba Freja; Faber, Jens Oscar; Nygaard, Birte

    2017-01-01

    Background Despite biochemical euthyroidism, some levothyroxine (L-T4)-treated hypothyroid patients report persisting symptoms and some of these patients are tentatively treated with a combination of L-T4 and liothyronine (L-T3). Combination therapy and the appropriate choice of blood tests to monitor treatment are highly debated among specialists and patients. Aim To evaluate whether measuring serum triiodothyronine (S-T3) at baseline or during combination therapy can be used as an indicator of a positive effect from L-T4/L-T3 combination therapy. Materials and Methods Observational retrospective study of patients (n = 42) with persisting symptoms of hypothyroidism despite L-T4 therapy who had normal TSH levels and did not have any comorbidities that could explain their symptoms. All were then treated with L-T4/L-T3 combination therapy at a dose ratio of 17/1 according to European Thyroid Association guidelines. Based on patient-reported outcome, they were divided into responders and nonresponders. Results Five patients were lost to follow-up and thus excluded. At the 3-month follow-up, 11 were classified as nonresponders and 26 as responders. At 12 months these figures had changed to 13 (35%) and 24 (65%), respectively. When comparing responders versus nonresponders, no differences were seen at baseline or during follow-up in S-T3 and in free T3 estimates. Further, logistic regression showed no correlation between S-T3 and free T3 estimates and responder/nonresponder status. Conclusion Our data indicate that serum T3 measurements are not suitable to predict which patient will benefit from L-T4/L-T3 combination therapy, and treatment response cannot be followed by repeated T3 measurements either. PMID:28589090

  14. Relationship between evaluation by quantitative fatty acid myocardial scintigraphy and response to beta-blockade therapy in patients with dilated cardiomyopathy.

    PubMed

    Ito, T; Hoshida, S; Nishino, M; Aoi, T; Egami, Y; Takeda, T; Kawabata, M; Tanouchi, J; Yamada, Y; Kamada, T

    2001-12-01

    Predicting the effect of beta-blockade therapy on the clinical outcome of patients with dilated cardiomyopathy (DCM) is difficult prior to the initiation of therapy. Myocardial fatty acid metabolism has been shown to be impaired in patients with DCM. We examined whether the extent of myocardial injury, as assessed by iodine-123 15-( p-iodophenyl)-3- R, S-methylpentadecanoic acid (BMIPP) myocardial scintigraphy, is related to the response of patients with DCM to beta-blockade therapy. Thirty-seven patients with DCM were examined using BMIPP myocardial scintigraphy before and after 6 months of treatment with metoprolol. Myocardial BMIPP uptake (%BM uptake) was estimated quantitatively as a percentage of the total injected count ratio. The left ventricular end-diastolic and end-systolic dimensions (LVDd, LVDs) and ejection fraction (LVEF) were also evaluated. The patients were divided into two groups according to their functional improvement (>10% elevation of LVEF) after 6 months of metoprolol therapy. Twenty-eight patients responded to the therapy, while nine did not. Prior to the therapy, no significant differences in LVDd, LVDs or LVEF were observed between the responders and non-responders. However, the %BM uptake was significantly lower in the non-responders than in the responders (1.0%+/-0.2% vs 2.1%+/-0.5%, P<0.001). The %BM uptake could be used to distinguish the responders from the non-responders with a sensitivity of 0.93 and a specificity of 1.00 at a threshold value of 1.4. After the metoprolol therapy, the %BM uptake improved significantly in the responders (2.5%+/-0.5%, P<0.01) but did not change in the non-responders. These results indicate that myocardial BMIPP uptake could predict the response of DCM patients to beta-blockade therapy.

  15. Would loss to follow-up bias the outcome evaluation of patients operated for degenerative disorders of the lumbar spine?

    PubMed Central

    2011-01-01

    Background and purpose Loss to follow-up may bias the outcome assessments of clinical registries. In this study, we wanted to determine whether outcomes were different in responding and non-responding patients who were included in a clinical spine surgery registry, at two years of follow-up. In addition, we wanted to identify risk factors for failure to respond. Methods 633 patients who were operated for degenerative disorders of the lumbar spine were followed for 2 years using a local clinical spine registry. Those who did not attend the clinic and those who did not answer a postal questionnaire—for whom 2 years of outcome data were missing—and who would be lost to follow-up according to the standard procedures of the registry protocols, were defined as non-respondents. They were traced and interviewed by telephone. Outcome measures were: improvement in health-related quality of life (EQ-5D), leg pain, and back pain; and also general state of health, employment status, and perceived benefits of the operation. Results We found no statistically significant differences in outcome between respondents (78% of the patients) and non-respondents (22%). Receipt of postal questionnaires (not being summoned for a follow-up visit) was the strongest risk factor for failure to respond. Forgetfulness appeared to be an important cause. Older patients and those who had complications were more likely to respond. Interpretation A loss to follow-up of 22% would not bias conclusions about overall treatment effects and, importantly, there were no indications of worse outcomes in non-respondents. PMID:21189113

  16. Association between resting jaw muscle electromyographic activity and mandibular advancement splint outcome in patients with obstructive sleep apnea.

    PubMed

    Ma, Serina Yok Ling; Whittle, Terry; Descallar, Joseph; Murray, Greg M; Darendeliler, M Ali; Cistulli, Peter; Dalci, Oyku

    2013-09-01

    The muscles of mastication are important in positioning the mandible and can therefore affect the patency of the upper airway. The aim of this study was to determine whether resting masticatory muscle activity influences the response to mandibular advancement splint treatment in patients with obstructive sleep apnea. Thirty-eight adult patients with obstructive sleep apnea were recruited for the study. Baseline electromyographic activities of the right anterior and posterior temporalis, masseter, and submandibular muscles were recorded with surface electrodes while the patients were awake, in the upright and supine positions, with the jaw in the postural position, and with and without a mandibular advancement splint. Muscle activity of the patients with obstructive sleep apnea was compared between responders (apnea-hypopnea index change ≥50%, and <10 events per hour) and nonresponders (apnea-hypopnea index change <50%) to mandibular advancement splint treatment. There were 18 responders and 20 nonresponders to mandibular advancement splint treatment. The responders had a trend for increased muscle activity in all muscle groups and scenarios. The resting muscle activity of the submandibular and masseter muscles while lying at rest and of the submandibular and posterior temporalis muscles while lying with the mandibular advancement splint in place were significantly greater (P <0.05) in the responders than in the nonresponders. Inherent baseline differences in muscle activity between responders and nonresponders to mandibular advancement splint treatment in adults with obstructive sleep apnea were observed. This preliminary study suggests that there might be a correlation between responsiveness with mandibular advancement splint treatment and baseline muscle activity. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  17. Presence of anti-HBc is associated to high rates of HBV resolved infection and low threshold for Occult HBV Infection in HIV patients with negative HBsAg in Chile.

    PubMed

    Vargas, Jose Ignacio; Jensen, Daniela; Sarmiento, Valeska; Peirano, Felipe; Acuña, Pedro; Fuster, Felipe; Soto, Sabrina; Ahumada, Rodrigo; Huilcaman, Marco; Bruna, Mario; Jensen, Werner; Fuster, Francisco

    2016-04-01

    HBV-HIV coinfection is prevalent. Frequently, anti-HBc is the only serological marker of HBV, which can be indicative of HBV resolved infection, when found together with anti-HBs reactivity; or present as "isolated anti-HBc," related to HBV occult infection with presence of detectable DNA HBV, more prevalent in HIV-positive individuals. Regional data about this condition are scarce. Anti-HBc rapid test has been used as screening, but its performance has not been described in HIV-positive patients. The aim of this study was determine prevalence of anti-HBc in HIV-positive patients, serological pattern of HBV resolved infection and isolated anti-HBc, evaluating presence of HBV occult infection. Assess anti-HBc rapid test compared to ECLIA. Methods included measurement of anti-HBc and anti-HBs in HIV-positive patients with negative HBsAg. Serum HBV DNA quantification and HBV booster vaccination to "isolated anti-HBc" individuals. Detection of anti-HBc by rapid test and ECLIA. In 192 patients, prevalence of anti-HBc was 42.7% (82/192); associated to male gender, drug use, men-sex-men, positive-VDRL, and longer time HIV diagnosis. 34.4% (66/192) had presence of anti-HBs, mean titers of 637 ui/ml. Isolated anti-HBc in 8.3% (16/192), associated to detectable HIV viral load and no-use of HAART; in them, HBV DNA was undetectable, and 60% responded to HBV vaccination booster. Anti-HBc rapid test showed low sensibility (32.9%) compared to ECLIA. These results show that prevalence of anti-HBc in HIV-positive individuals is high, in most cases accompanied with anti-HBs as HBV resolved infection. Low prevalence of "isolated anti-HBc," with undetectable HBV DNA, and most had anamnestic response to HBV vaccination; suggest low possibility of occult HBV infection. Anti-HBc rapid test cannot be recommended as screening method for anti-HBc.

  18. Consensus Interferon Plus Ribavirin for Hepatitis C Genotype 3 Patients Previously Treated With Pegylated Interferon Plus Ribavirin

    PubMed Central

    Abbas, Zaigham; Tayyab, Ghiasun Nabi; Qureshi, Mustafa; Memon, Mohammad Sadik; Subhan, Amna; Shakir, Tanzila; Jafri, Wasim; Hamid, Saeed

    2013-01-01

    Background Not enough data are available about the effectiveness of consensus interferon (CIFN) among HCV genotype 3 patients who failed to respond to pegylated interferon and ribavirin. Objectives We aimed to assess the efficacy and safety of CIFN and ribavirin in non-responders and relapsers to pegylated interferon with ribavirin therapy. Patients and Methods This open-label investigator-initiated study included 44 patients who received CIFN 15 µg /day plus ribavirin 800-1200 mg daily. In patients with an early virological response (EVR), the dose of CIFN was reduced to 15 µg thrice a week for further 36 weeks. Patients with delayed virological response continued to receive daily CIFN plus ribavirin to complete 48 weeks. The patients were considered “non-responders” if there were less than 2 log reduction in HCV RNA at 12 weeks and detectable HCV RNA at 24 weeks. Results Twenty-four patients (55%) were non-responders and 20 patients were relapsers to the previous treatment with pegylated interferon plus ribavirin (mean age 43.6 ± 9.4 years, males 25 (57%)). Nine patients were clinically cirrhotic (Child A). End of treatment virological response was achieved in 19 (43.1%) patients and sustained virological response (SVR) occurred in 12 (27.3%). Out of these 12 patients, eight were non-responders and four were relapsers to the previous treatment. Advanced fibrosis or clinical cirrhosis was associated with low SVR. Adverse events were fever, myalgia, anorexia, depression, and weight loss. Two patients received granulocyte colony stimulating factor for transient neutropenia. Seven patients were given erythropoietin to improve hemoglobin, and six were treated for mild depression. Two patients developed portosystemic encephalopathy. Conclusions More than one-quarter of treatment-experienced patients with HCV genotype 3 achieved SVR after re-treatment with consensus interferon plus ribavirin. PMID:24358041

  19. A randomized trial of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in the re-treatment of patients with chronic hepatitis C not responding to standard interferon and ribavirin.

    PubMed

    Ciancio, A; Picciotto, A; Giordanino, C; Smedile, A; Tabone, M; Manca, A; Marenco, G; Garbagnoli, P; Andreoni, M; Cariti, G; Calleri, G; Sartori, M; Cusumano, S; Grasso, A; Rizzi, R; Gallo, M; Basso, M; Anselmo, M; Percario, G; Ciccone, G; Rizzetto, M; Saracco, G

    2006-10-01

    There is yet no established treatment for chronic hepatitis C patients non-responder to standard interferon and ribavirin. To evaluate efficacy and safety of pegylated-interferon-alpha2a plus ribavirin with or without amantadine in such patients. 161 non-responders to standard interferon and ribavirin were randomized into two groups: 81 patients (Group 1) were given weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily for 12 months, 80 patients (Group 2) received weekly Peg-IFN-alpha2a 180 microg plus ribavirin 1,000-1,200 mg/daily and amantadine 200 mg/daily for 12 months. At the end of follow-up, HCV-RNA was negative in 29.6% of Group 1 and in 21.2% of Group 2 patients (P = 0.22). Patients with genotypes 1 and 4 responded better to bi-therapy (21.7%) than to triple therapy (17.3%, P = 0.5) while among patients with genotypes 2 and 3 there was a trend towards a higher sustained virological response rate when retreated with triple treatment (80% vs. 75%, P = 0.82). On multivariate analysis, genotype 1 or 4, high body mass index and >20% reduction of Peg-interferon were associated with the treatment failure. The addition of amantadine does not improve the overall SVR rate in non-responder patients retreated with Peg-IFN and ribavirin; however, about 30% of non-responders may achieve a sustained response, in particular patients with genotypes 2 and 3 show a high SVR (75%).

  20. Surgical castration efficiently delays the time of starting a systemic chemotherapy in castration-resistant prostate cancer patients refractory to initial androgen-deprivation therapy

    PubMed Central

    Kang, Minyong; Lee, Sangchul; Oh, Jong Jin; Hong, Sung Kyu; Lee, Sang Eun; Byun, Seok-Soo

    2015-01-01

    Background The aim of this study was to investigate the effects of surgical castration, particularly delaying the time to entrance of systemic chemotherapy, in castration-resistant prostate cancer (CRPC) patients who were refractory to initial combination androgen deprivation therapy. Materials and methods We analyzed the clinical data of 14 CRPC patients diagnosed at Seoul National University Bundang Hospital (SNUBH) from November 2008 through May 2015. After exclusion of three patients, we finally analyzed the baseline characteristics of 11 CRPC patients. We also assessed the delaying time of docetaxel administration, which was defined as response duration, after surgical castration. Results After bilateral orchiectomy, the treatment response rate was 45.4% and the median duration of response was 9 months (range 4–48 mo). Responders had less aggressive biopsy Gleason scores compared to nonresponders. Notably, responders showed the reducing pattern of serum prostate specific antigen levels, while nonresponders demonstrated increasing tendency after surgical castration. Moreover, responders also presented with a reduction pattern of serum testosterone levels, whereas nonresponders showed an increasing pattern of testosterone levels after bilateral orchiectomy. Conclusions In summary, despite the limited number of cases for convincing evidence, our results shed light again on the clinical benefits of surgical castration prior to the systemic chemotherapy in some CRPC patients after initial hormone therapy. PMID:26779458

  1. The prevalence and drug sensitivity of tuberculosis among patients dying in hospital in KwaZulu-Natal, South Africa: a postmortem study.

    PubMed

    Cohen, Ted; Murray, Megan; Wallengren, Kristina; Alvarez, Gonzalo G; Samuel, Elizabeth Y; Wilson, Douglas

    2010-06-22

    Tuberculosis is the leading cause of death in South Africa by death notification, but accurate diagnosis of tuberculosis is challenging in this setting of high HIV prevalence. We conducted limited autopsies on young adults dying in a single public hospital in the province of KwaZulu-Natal between October 2008 and August 2009 in order to estimate the magnitude of deaths attributable to tuberculosis. We studied a representative sample of 240 adult inpatients (aged 20-45 years) dying after admission to Edendale Hospital. Limited autopsies included collection of respiratory tract secretions and tissue by needle core biopsies of lung, liver, and spleen. Specimens were examined by fluorescent microscopy for acid-fast bacilli and cultured in liquid media; cultures positive for M. tuberculosis were tested for drug susceptibility to first- and second-line antibiotics. Ninety-four percent of our study cohort was HIV seropositive and 50% of decedents had culture-positive tuberculosis at the time of death. Fifty percent of the participants were on treatment for tuberculosis at the time of death and 58% of these treated individuals remained culture positive at the time of death. Of the 50% not receiving tuberculosis treatment, 42% were culture positive. Seventeen percent of all positive cultures were resistant to both isoniazid and rifampin (i.e., multidrug resistant); 16% of patients dying during the initiation phase of their first ever course of tuberculosis treatment were infected with multidrug-resistant bacilli. Our findings reveal the immense toll of tuberculosis among HIV-positive individuals in KwaZulu-Natal. The majority of decedents who remained culture positive despite receiving tuberculosis treatment were infected with pan-susceptible M. tuberculosis, suggesting that the diagnosis of tuberculosis was made too late to alter the fatal course of the infection. There is also a significant burden of undetected multidrug-resistant tuberculosis among HIV-coinfected

  2. The Prevalence and Drug Sensitivity of Tuberculosis among Patients Dying in Hospital in KwaZulu-Natal, South Africa: A Postmortem Study

    PubMed Central

    Cohen, Ted; Murray, Megan; Wallengren, Kristina; Alvarez, Gonzalo G.; Samuel, Elizabeth Y.; Wilson, Douglas

    2010-01-01

    -resistant tuberculosis among HIV-coinfected individuals dying in this setting. New public health approaches that improve early diagnosis of tuberculosis and accelerate the initiation of treatment are urgently needed in this setting. Please see later in the article for the Editors' Summary PMID:20582324

  3. Role of opsonins in clinical response to granulocyte transfusion in granulocytopenic patients

    SciTech Connect

    Keusch, G.T.; Ambinder, E.P.; Kovacs, I.; Goldberg, J.D.; Phillips, D.M.; Holland, J.F.

    1982-10-01

    Fifty febrile severely granulocytopenic patients were given four daily transfusions of 2.2 X 10(10) normal donor granulocytes. Twenty-three responded clinically, although both responders and nonresponders were similar in clinical characteristics at the outset. This study examines the relation between serum opsonic activity before initiation of granulocyte administration and clinical response. Opsonic activity to three test organisms (Escherichia coli 286 and ON 2, and Staphylococcus aureus) and to 15 blood stream isolates from 14 patients was measured as serum-dependent uptake of heat-killed /sup 14/C-labeled bacteria by normal donor leukopheresis granulocytes in an in vitro assay and compared with results obtained with a standard normal serum in each assay. At a concentration of 8 percent serum, all patient groups were equivalent to standard for the three test organisms. When rate-limiting concentrations of serum were employed, opsonic activity remained similar to standard for S. aureus in all patient groups and for the two E. coli strains in responders. In contrast, opsonins for E. coli decreased to 41 to 50 percent of standard in nonresponders. When patients with proved infection were separately analyzed, opsonin activity for E. coli was significantly greater in responders than nonresponders. Eight of 10 patients with 75 percent or greater of standard for opsonic activity against their own blood stream isolates also responded, whereas zero of four with less than 75 percent of standard had a favorable outcome. These results indicate that serum opsonic activity may be a determinant of clinical response to granulocyte transfusion in infected granulocytopenic patients. We conclude that opsonic activity should be assessed in such patients before granulocyte administration and suggest a trial of plasma infusion in opsonin-deficient patients.

  4. Do Patient Profiles Influence the Effects of Massage? A Controlled Clinical Trial.

    PubMed

    Díaz-Rodríguez, Lourdes; Fernández-Pérez, Antonio Manuel; Galiano-Castillo, Noelia; Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Martín-Martín, L M; Arroyo-Morales, Manuel

    2016-10-01

    Considerable scientific evidence has been published on the effectiveness of massage in different conditions, but it remains unclear whether this effectiveness is modulated by the profile of patients. The aim of this study was to compare the effects of a 21-min myofascial therapy protocol on stress responders and nonresponders stressed in the laboratory with a cold pressor test. Dependent variables included heart rate variability (HRV), blood pressure, and salivary markers such as flow rate, cortisol, immunoglobulin A (IgA), and α-amylase activity. A controlled, repeated measures, single-blind trial was conducted in 30 Caucasian students with a mean (SD) age of 20.70 (4.50) years. We found no significant between-group differences in descriptive characteristics or in any preintervention outcome measure. Analysis of covariance revealed significant increases in HRV index (F = 0.18, p = .01), salivary flow rate (F = 0.16, p = .02), and salivary IgA concentration (F = 4.36, p = .04) and significant decreases in the low-frequency domain (F = 0.18, p = .04) and LF-high-frequency ratio (F = 0.18, p = .01) in the stress responder group in comparison to the nonresponder group. In conclusion, a better response to massage was observed in stress responders than in nonresponders across various HRV parameters and salivary measures.

  5. A comparison between augmentation with olanzapine and increased risperidone dose in acute schizophrenia patients showing early non-response to risperidone.

    PubMed

    Hatta, Kotaro; Otachi, Taro; Sudo, Yasuhiko; Kuga, Hironori; Takebayashi, Hiroshi; Hayashi, Hideaki; Ishii, Ryusuke; Kasuya, Masataka; Hayakawa, Tatsuro; Morikawa, Fumiyoshi; Hata, Kazuya; Nakamura, Mitsuru; Usui, Chie; Nakamura, Hiroyuki; Hirata, Toyoaki; Sawa, Yutaka

    2012-07-30

    We examined whether augmentation with olanzapine would be superior to increased risperidone dose among acute schizophrenia patients showing early non-response to risperidone. We performed a rater-blinded, randomized controlled trial at psychiatric emergency sites. Eligible patients were newly admitted patients with acute schizophrenia. Early response was defined as Clinical Global Impressions-Improvement Scale score ≤3 following 2 weeks of treatment. Early non-responders were allocated to receive either augmentation with olanzapine (RIS+OLZ group) or increased risperidone dose (RIS+RIS group). The 78 patients who completed 2 weeks of treatment were divided into 52 early responders to risperidone and 26 early non-responders to risperidone (RIS+OLZ group, n=13; RIS+RIS group, n=13). No difference in the achievement of ≥50% improvement in Positive and Negative Syndrome Scale total score was observed between RIS+OLZ and RIS+RIS groups. Although time to treatment discontinuation for any cause was significantly shorter in the RIS+RIS group (6.8 weeks [95% confidence interval, 5.2-8.4]) than in early responders to risperidone (8.6 weeks [7.9-9.3]; P=0.018), there was no significant difference between the RIS+OLZ group (7.9 weeks [6.3-9.5]) and early responders to risperidone. Secondary outcomes justify the inclusion of augmentation arms in additional, larger studies comparing strategies for early non-responders.

  6. Value of percent change in tumoral volume measured at T2 -weighted and diffusion-weighted MRI to identify responders after neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma.

    PubMed

    Quaia, Emilio; Gennari, Antonio Giulio; Ricciardi, Maria Chiara; Ulcigrai, Veronica; Angileri, Roberta; Cova, Maria Assunta

    2016-12-01

    To evaluate the percent change in tumoral volume measured at T2 -weighted magnetic resonance imaging (T2 WMRI) and diffusion-weighted (DWI) as a method to identify responders after chemo- and radiation therapy (CRT) in patients with locally advanced rectal carcinoma. Forty-five consecutive patients (mean age ± SD: 72 years ± 9.7; male/female = 24/21) with locally advanced rectal carcinoma underwent CRT followed by surgery. Each patient underwent T2 WMRI and DWI at 1.5T before and 6 weeks after the completion of CRT. The percent change in tumoral volume before and 6 weeks after CRT was compared in patients classified as responders and nonresponders according to rectal cancer regression grade. Twenty-five patients were classified as responders with either partial (n = 20) or complete response (n = 5), while 20 patients were classified as nonresponders due to stable disease (n = 18) or disease progression (n = 2). Responders vs. nonresponders differed in the percent change of tumoral volume at T2 WMRI (-67% ± 26% vs. -29% ± 26%; P < 0.05) and DWI images (-72% ± 24% vs. -33% ± 28%; P < 0.05) with a cutoff ≤ -70% for T2 WMRI (sensitivity = 69%, 95% confidence interval [CI]: 48-85%; specificity = 100%, 95% CI 81-100%) and ≤66% for DWI (sensitivity = 73%, 95% CI: 52-88%; specificity = 100%, 95% CI 81-100%). The percent change in tumoral volume at T2 WMRI and DWI images can differentiate responders from nonresponders in patients with locally advanced rectal carcinoma after neoadjuvant CRT. J. Magn. Reson. Imaging 2016;44:1415-1424. © 2016 International Society for Magnetic Resonance in Medicine.

  7. Quantitative ultrasound evaluation of tumor cell death response in locally advanced breast cancer patients receiving chemotherapy.

    PubMed

    Sadeghi-Naini, Ali; Papanicolau, Naum; Falou, Omar; Zubovits, Judit; Dent, Rebecca; Verma, Sunil; Trudeau, Maureen; Boileau, Jean Francois; Spayne, Jacqueline; Iradji, Sara; Sofroni, Ervis; Lee, Justin; Lemon-Wong, Sharon; Yaffe, Martin; Kolios, Michael C; Czarnota, Gregory J

    2013-04-15

    Quantitative ultrasound techniques have been recently shown to be capable of detecting cell death through studies conducted on in vitro and in vivo models. This study investigates for the first time the potential of early detection of tumor cell death in response to clinical cancer therapy administration in patients using quantitative ultrasound spectroscopic methods. Patients (n = 24) with locally advanced breast cancer received neoadjuvant chemotherapy treatments. Ultrasound data were collected before treatment onset and at 4 times during treatment (weeks 1, 4, and 8, and preoperatively). Quantitative ultrasound parameters were evaluated for clinically responsive and nonresponding patients. Results indicated that quantitative ultrasound parameters showed significant changes for patients who responded to treatment, and no similar alteration was observed in treatment-refractory patients. Such differences between clinically and pathologically determined responding and nonresponding patients were statistically significant (P < 0.05) after 4 weeks of chemotherapy. Responding patients showed changes in parameters related to cell death with, on average, an increase in mid-band fit and 0-MHz intercept of 9.1 ± 1.2 dBr and 8.9 ± 1.9 dBr, respectively, whereas spectral slope was invariant. Linear discriminant analysis revealed a sensitivity of 100% and a specificity of 83.3% for distinguishing nonresponding patients by the fourth week into a course of chemotherapy lasting several months. This study reports for the first time that quantitative ultrasound spectroscopic methods can be applied clinically to evaluate cancer treatment responses noninvasively. The results form a basis for monitoring chemotherapy effects and facilitating the personalization of cancer treatment.

  8. Effect of thymidylate synthase (TYMS) gene polymorphisms with methotrexate treatment outcome in south Indian Tamil patients with rheumatoid arthritis.

    PubMed

    Muralidharan, Niveditha; Misra, Durga P; Jain, Vikramraj K; Negi, Vir Singh

    2017-03-27

    Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease causing joint damage and significant functional impairment. Methotrexate (MTX) remains the mainstay for the treatment of RA. MTX inhibits several enzymes of the folate and nucleotide pathways. Thymidylate synthase (TYMS) is an important enzyme in the de novo pyrimidine pathway responsible for DNA replication. The two common gene polymorphisms analyzed in TYMS are 28-bp tandem repeat polymorphism and a 6-bp insertion/deletion polymorphism. The present study was carried out to find the role of these TYMS gene polymorphisms with clinical phenotype, treatment response, and MTX adverse events in 254 patients with RA of south Indian Tamil ethnicity. TYMS gene polymorphisms were analyzed by PCR. The allele frequencies of TYMS gene polymorphisms did not differ between good and non-responders. However, the TYMS 28-bp tandem repeat 3R allele was higher in non-responders than in patients undergoing remission [64 vs 51.11%, p = 0.06, OR 0.58, 95% CI (0.34-1.00)]. The TYMS 6-bp deletion allele was higher in non-responders than good responders [78.20 vs 64.92%, p = 0.06, OR 0.51 95% CI (0.27-0.98)]. TYMS 3R allele and TYMS 6-bp deletion allele may favor non-response to MTX in south Indian Tamils. TYMS gene polymorphisms did not influence MTX adverse events.

  9. Immune reconstitution inflammatory syndrome in HIV and sporotrichosis coinfection: report of two cases and review of the literature.

    PubMed

    Lyra, Marcelo Rosandiski; Nascimento, Maria Letícia Fernandes Oliveira; Varon, Andréa Gina; Pimentel, Maria Inês Fernandes; Antonio, Liliane de Fátima; Saheki, Maurício Naoto; Bedoya-Pacheco, Sandro Javier; Valle, Antonio Carlos Francesconi do

    2014-01-01

    We report 2 cases of patients with immune reconstitution inflammatory syndrome (IRIS) associated with cutaneous disseminated sporotrichosis and human immunodeficiency virus (HIV) coinfection. The patients received specific treatment for sporotrichosis. However, after 4 and 5 weeks from the beginning of antiretroviral therapy, both patients experienced clinical exacerbation of skin lesions despite increased T CD4+ cells (T cells cluster of differentiation 4 positive) count and decreased viral load. Despite this exacerbation, subsequent mycological examination after systemic corticosteroid administration did not reveal fungal growth. Accordingly, they were diagnosed with IRIS. However, the sudden withdrawal of the corticosteroids resulted in the recurrence of IRIS symptoms. No serious adverse effects could be attributed to prednisone. We recommend corticosteroid treatment for mild-to-moderate cases of IRIS in sporotrichosis and HIV coinfection with close follow-up.

  10. HBV virological suppression: still not enough to save from hepatocellular carcinoma. A case report on a 15-year, real-life story

    PubMed

    Prestileo, Tullio; Di Lorenzo, Francesco; Sanfilippo, Adriana; Imburgia, Claudia; Cabibbo, Giuseppe; Corrao, Salvatore

    2017-09-01

    Among HIV-infected patients worldwide, 2-4 million are chronically infected with HBV. We report a 15-year, real-life story of a patient with HBV-HIV coinfection, who developed HCC despite high treatment adherence and complete viral suppression. The aim of our report is to alert the infectious diseases community to monitor the possible development of HCC regardless of high treatment adherence and complete viral suppression.

  11. Extra-pulmonary manifestations of paracoccidioidomycosis associated with acquired immunodeficiency syndrome: a case report*

    PubMed Central

    Safe, Izabella Picinin; do Valle, Fabio Francesconi; Maia, Daniela Cristina Caetano; Agonio, Bárbara; Monte, Rossicléia Lins; Araújo, José de Ribamar; Cordeiro-Santos, Marcelo

    2014-01-01

    We present a patient with Paracoccidioidomycosis/HIV coinfection which has been investigated because of chronic monoarthritis and mucocutaneous lesions. A biopsy of the synovial membrane and skin revealed structures consistent with Paracoccidioides brasiliensis. At diagnosis, the count of CD4 + T cells was 44 cells/mm3. We emphasize the importance of clinical suspicion of Paracoccidioidomycosis in patients with HIV/AIDS who live in or are from risk areas. PMID:24626662

  12. Costs associated with failure to respond to treatment among patients with rheumatoid arthritis initiating TNFi therapy: a retrospective claims analysis.

    PubMed

    Grabner, Michael; Boytsov, Natalie N; Huang, Qing; Zhang, Xiang; Yan, Tingjian; Curtis, Jeffrey R

    2017-05-15

    Tumor necrosis factor inhibitors (TNFi) are common second-line treatments for rheumatoid arthritis (RA). This study was designed to compare the real-world clinical and economic outcomes between patients with RA who responded to TNFi therapy and those who did not. For this retrospective cohort analysis we used medical and pharmacy claims from members of 14 large U.S. commercial health plans represented in the HealthCore Integrated Research Database. Adult patients (aged ≥18 years) diagnosed with RA and initiating TNFi therapy (index date) between 1 January 2007 and 30 April 2014 were included in the study. Treatment response was assessed using a previously developed and validated claims-based algorithm. Patients classified as treatment responders in the 12 months postindex were matched 1:1 to nonresponders on important baseline characteristics, including sex, age, index TNFi agent, and comorbidities. The matched cohorts were then compared on their all-cause and RA-related healthcare resource use, and costs were assessed from a payer perspective during the first, second, and third years postindex using parametric tests, regressions, and a nonparametric bootstrap. A total of 7797 patients met the study inclusion criteria, among whom 2337 (30%) were classified as treatment responders. The responders had significantly lower all-cause hospitalizations, emergency department visits, and physical/occupational therapy visits than matched nonresponders during the first-year postindex. Mean total all-cause medical costs were $5737 higher for matched nonresponders, largely driven by outpatient visits and hospitalizations. Mean all-cause pharmacy costs (excluding costs of biologics) were $354 higher for matched nonresponders. Mean RA-related pharmacy costs (conventional synthetic and biologic drugs), however, were $8579 higher in the responder cohort, driven by higher adherence to their index TNFi agent (p < 0.01 for all comparisons). A similar pattern of cost

  13. Notes from the field: repeat syphilis infection and HIV coinfection among men who have sex with men--Baltimore, Maryland, 2010-2011.

    PubMed

    2013-08-16

    Syphilis diagnoses in the United States have increased substantially over the past decade, and most cases occurred among men who have sex with men (MSM). Nationally, rates of primary and secondary (P&S) syphilis reported among men increased, from 3.0 cases per 100,000 population in 2001 to 8.2 in 2011. In 2011, approximately 72% of P&S syphilis cases occurred among MSM*, among whom new diagnoses of human immunodeficiency virus (HIV) infection have increased in recent years. Infection with syphilis increases the likelihood of acquiring and transmitting HIV; moreover, the occurrence of syphilis in an HIV-infected person is an indication of behavior that might increase the likelihood of HIV transmission. The population of Baltimore, Maryland, is particularly affected by syphilis and HIV. In 2011, the Baltimore metropolitan statistical area (MSA) had the second highest rate of reported cases of P&S syphilis (11.4 per 100,000 population) and the sixth highest estimated rate of diagnoses of HIV infection (33.8 per 100,000 population) compared with other MSAs in the United States. Local public health officials have noted a subpopulation of MSM diagnosed with repeat syphilis infection; they believe that this subpopulation might bear a disproportionate burden of both syphilis and HIV infection and that intensifying syphilis and HIV prevention efforts among this subpopulation might reduce syphilis and HIV transmission overall in the Baltimore area.

  14. Development of a pigtail macaque model of sexually transmitted infection/HIV coinfection using Chlamydia trachomatis, Trichomonas vaginalis, and SHIVSF162P3

    PubMed Central

    Henning, Tara; Fakile, Yetunde; Phillips, Christi; Sweeney, Elizabeth; Mitchell, James; Patton, Dorothy; Sturdevant, Gail; Caldwell, Harlan D.; Secor, W. Evan; Papp, John; Hendry, R. Michael; McNicholl, Janet; Kersh, Ellen

    2012-01-01

    Background Sexually transmitted infections (STIs) are associated with an increased risk of HIV infection. To model the interaction between STIs and HIV infection, we evaluated the capacity of the pigtail macaque model to sustain triple infection with Trichomonas vaginalis, Chlamydia trachomatis, and SHIVSF162P3. Methods Seven SHIVSF162P3-infected pigtail macaques were inoculated with T. vaginalis only (n = 2), C. trachomatis only (n = 1), both T. vaginalis and C. trachomatis (n = 2), or control media (no STI; n = 2). Infections were confirmed by culture and/or nucleic acid testing. Genital mucosa was visualized by colposcopy. Results Characteristic gynecologic signs were observed for both STIs, but not in control animals. Manifestations were most prominent at days 7–10 post-infection. STIs persisted between 4 and 6 weeks and were cleared with antibiotics. Conclusions These pilot studies demonstrate the first successful STI-SHIV triple infection of pigtail macaques, with clinical presentation of genital STI symptoms similar to those observed in humans. PMID:21781129

  15. Biological markers of mesenchymal stromal cells as predictors of response to autologous stem cell transplantation in patients with amyotrophic lateral sclerosis: an investigator-initiated trial and in vivo study.

    PubMed

    Kim, Hyun Young; Kim, Heejaung; Oh, Ki-Wook; Oh, Seong-Il; Koh, Seong-Ho; Baik, Wonki; Noh, Min Young; Kim, Kyung Suk; Kim, Seung Hyun

    2014-10-01

    Bone marrow mesenchymal stromal cells (MSCs) can modify disease progression in amyotrophic lateral sclerosis (ALS) model. However, there are currently no accurate biological markers for predicting the efficacy of autologous MSC transplants in ALS patients. This open-label, single-arm, investigator-initiated clinical study was designed to identify markers of MSCs that could be used as potential predictors of response to autologous MSC therapy in patients with ALS. We enrolled 37 patients with ALS who received autologous MSCs via intrathecal injection in two monthly doses. After a 6-month follow-up period, the patients were categorized as responders and non-responders based on their scores on the revised ALS Functional Rating Scale (ALSFRS-R). Biological markers including β-fibroblast growth factor-2, stromal cell-derived factor-1α, vascular endothelial growth factor (VEGF), insulin-like growth factor-1, brain-derived neurotrophic factor, angiogenin (ANG), interleukin (IL)-4, IL-10, and transforming growth factor-β (TGF-β) were measured in the MSC cultures and their levels were compared between the responders and nonresponders. To confirm the markers' predictive ability, MSCs isolated from one patient in each group were transplanted into the cisterna magna of mutant SOD1(G93A) transgenic mice to measure their lifespans, locomotor activity, and motor neuron numbers. The levels of VEGF, ANG, and TGF-β were significantly higher in responders than in nonresponders. In the mouse model, the recipients of responder MSCs had a significantly slower onset of symptoms and a significantly longer lifespan than the recipients of nonresponders or controls. Our data suggest that VEGF, ANG, and TGF-β levels in MSCs could be used as potential biological markers to predict the effectiveness of autologous MSC therapy and to identify those patients who could optimally benefit from MSC treatment. © 2014 AlphaMed Press.

  16. Role of Right Ventricular Dysfunction and Diabetes Mellitus in N-terminal pro-B-type Natriuretic Peptide Response of Patients With Severe Mitral Regurgitation and Heart Failure After MitraClip.

    PubMed

    Kaneko, Hidehiro; Neuss, Michael; Weissenborn, Jens; Butter, Christian

    2017-04-06

    MitraClip (MC) is an alternative therapeutic option for patients with severe mitral regurgitation (MR) who are at high surgical risk. Most candidates for MC have severe heart failure (HF) with increased N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels. We sought to clarify the response of NT-pro BNP after MC and to identify the determinants of NT-pro BNP nonresponders. Among 136 consecutive patients successfully treated with MC, we excluded 20 patients due to low baseline NT-pro BNP levels and therefore examined 116 patients. NT-pro BNP responders were defined as patients whose NT-pro BNP levels decreased by > 30% at 6 months after MC. Mean NT-pro BNP levels significantly decreased from 6,117 pg/mL at baseline to 4,143 pg/mL at 6 months after MC (P < 0.001); 61 patients (53%) were responders. Diabetes mellitus (DM) (51% versus 25%; P = 0.003) and atrial fibrillation (67% versus 49%; P = 0.049) were more common in nonresponders. Baseline New York Heart Association (NYHA) class and NT-proBNP levels were higher in responders. Right ventricular systolic dysfunction (RVSD) defined as tricuspid annular plane systolic excursion (TAPSE) < 15 mm was more common in nonresponders (41% versus 18%; P = 0.008). Multivariable logistic regression analysis revealed that DM (odds ratio [OR], 2.966; P = 0.014), RVSD (OR, 3.948; P = 0.006), and baseline NT-proBNP > 5,000 pg/mL (OR, 0.204; P = 0.001) were independent determinants of nonresponders. All-cause death tended to be less common in responders to NT-pro BNP (20% versus 31%; P = 0.163). In conclusion, NT-pro BNP levels significantly decreased after MC. DM and RVSD were determinants of NT-pro BNP nonresponse after the MC procedure.

  17. Day surgery; development of a questionnaire for eliciting patients' experiences.

    PubMed

    Black, N; Sanderson, C

    1993-09-01

    To develop a single, short, acceptable, and validated postal questionnaire for assessing patients' experiences of the process and outcome of day surgery. Interviews and review of existing questionnaires; piloting and field testing of draft questionnaires; consistency and validity checks. Four hospitals, in Coventry (two), Swindon, and Milton Keynes. 373 patients undergoing day surgery in 1990. Postoperative symptoms, complications, health and functional status, general satisfaction, and satisfaction with specific aspects of care. Response rates of 50% were obtained on field testing draft questionnaires preoperatively and one week and one month after surgery. 28% of initial non-responders replied on receiving a postal reminder, regardless of whether or not a duplicate questionnaire was sent; a second reminder had little impact. Many patients who expressed overall satisfaction with their care were nevertheless dissatisfied with some specific aspects. Outcome and satisfaction were related to three aspects of case mix; patient's age, sex, and type of operative procedure. The final questionnaire produced as a result of this work included 28 questions with precoded answers plus opportunities to provide qualitative comments. Several factors (only one, shorter questionnaire to complete, fewer categories of nonresponders, and administration locally) suggested that a response rate of at least 65% (with one postal reminder) could be expected. A validated questionnaire for day surgery was developed, which will be used to establish a national comparative database.

  18. Improved control of osteoarthritis pain and self-reported health status in non-responders to celecoxib switched to rofecoxib: results of PAVIA, an open-label post-marketing survey in Spain.

    PubMed

    Collantes-Estevez, Eduardo; Fernandez-Perez, Cristina

    2003-01-01

    An open-label multicentre study was conducted in primary care centres in Spain to investigate the effect of a switch from celecoxib to rofecoxib among patients with osteoarthritis and to identify factors associated with a good response to rofecoxib treatment. Patients were eligible to participate in this study if their physicians considered that they might benefit from such a change of therapy. A total of 2,228 patients (1481 women) were enrolled in the study: participants' mean age was 66.37 years (SD 9.04). Mean duration of OA was 7.44 (6.38) years. Predominant sites of OA included the knee (1,132 patients, 50.8%), lumbar spine (977 patients, 43.9%) and cervical spine (739 patients, 33.2%). At baseline, most patients (77%) were being prescribed celecoxib 200 mg/day; during the study most (92.5%) received rofecoxib 25 mg/day. The mean interval between switch to rofecoxib and follow-up interview was 33 days. Patients considered the therapeutic response to rofecoxib substantially and significantly superior to that previously obtained with celecoxib for the management of OA-related pain and OA-related health status (p < 0.001). Seventy-two percent of patients classified their response to rofecoxib therapy as 'good' or 'very good' (vs 6.6% of patients at baseline with celecoxib) and 89.3% of patients expressed satisfaction with rofecoxib (vs 28.9% at baseline with celecoxib). Improvements reported in patient self-assessments following rofecoxib therapy were complemented by similar changes in physician perceptions. The number of patients considered by their doctors to have 'good' or 'very good' OA-related health status rose from 10.1% at baseline to 80.0% on completion of rofecoxib therapy. Ancillary indices such as the proportion of patients with self-reported depression were also favourably influenced by the switch to rofecoxib from celecoxib. Determinants of response: Patient characteristics identified in multivariate analysis as predictive of a favourable response

  19. Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV.

    PubMed

    Rockstroh, Jürgen Kurt

    2017-04-01

    Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.

  20. Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy

    PubMed Central

    Baird, Angela C; Mallon, Dominic; Radford-Smith, Graham; Boyer, Julien; Piche, Thierry; Prescott, Susan L; Lawrance, Ian C; Tulic, Meri K

    2016-01-01

    AIM To study the innate immune function in ulcerative colitis (UC) patients who fail to respond to anti-tumor necrosis factor (TNF) therapy. METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell (PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor (TLR) expression and cytokine production post TLR stimulation was assessed in UC “responders” (n = 12) and “non-responders” (n = 12) and compared to healthy controls (n = 12). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory (TNF, IL-1β, IL-6), immuno-regulatory (IL-10), Th1 (IL-12, IFNγ) and Th2 (IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS. RESULTS Prior to anti-TNF therapy, responders and non-responders had similar level of disease severity and activity. PBMC’s ability to respond to TLR stimulation was not affected by TNF therapy, patient’s severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders (P < 0.05). Following TLR stimulation, non-responders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls (P < 0.01) and diminished TNF (P < 0.001) and IL-1β (P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells (pDCs) (P < 0.01) but increased number of CD4+ regulatory T cells (Tregs) (P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2, -4 and -7 activation (P < 0.001). CONCLUSION Reduced innate immunity in

  1. Dynamic contrast-enhanced perfusion area detector CT for non-small cell lung cancer patients: Influence of mathematical models on early prediction capabilities for treatment response and recurrence after chemoradiotherapy.

    PubMed

    Ohno, Yoshiharu; Koyama, Hisanobu; Fujisawa, Yasuko; Yoshikawa, Takeshi; Seki, Shinichiro; Sugihara, Naoki; Sugimura, Kazuro

    2016-01-01

    To determine the capability and influence of the mathematical method on dynamic contrast-enhanced (CE-) perfusion area detector CT (ADCT) for early prediction of treatment response as well as progression free and overall survival (PFS and OS) of non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy. Sixty-six consecutive stage III NSCLC patients underwent dynamic CE-perfusion ADCT examinations, chemoradiotherapy and follow-up examinations. Response Evaluation Criteria in Solid Tumors (RECIST) criteria were used to divide all patients into responders and non-responders. Differences in each of the indices for all targeted lesions between measurements obtained 2 weeks prior to the first and the third course of chemotherapy were determined for all patients. ROC analyses were employed to determine the capability of perfusion indices as markers for distinguishing RECIST responders from non-responders. To evaluate their capability for early prediction of therapeutic effect, OS of perfusion index-based responders and non-responders were compared by using the Kaplan-Meier method followed by log-rank test. Area under the curve (Az) for total perfusion by means of the dual-input maximum slope method was significantly larger than that of pulmonary arterial perfusion using the same method (p=0.007) and of perfusion with the single-input maximum slope method (p=0.007). Mean OS demonstrated significantly difference between responder- and non-responder groups for total perfusion (p=0.02). Mathematical models have significant influence on assessment for early prediction of treatment response, disease progression and overall survival using dynamic CE-perfusion ADCT for NSCLC patients treated with chemoradiotherapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. Hepatitis C virus infection and risk of cancer: a population-based cohort study

    PubMed Central

    Omland, Lars Haukali; Farkas, Dora Körmendiné; Jepsen, Peter; Obel, Niels; Pedersen, Lars

    2010-01-01

    Background: Hepatitis C virus (HCV) infection is associated with an increased risk of primary liver cancer; however, 5- and 10-year risk estimates are needed. The association of HCV with non-Hodgkin lymphoma (NHL) is uncertain and the association with other cancers is unknown. Method: We conducted a nationwide, population-based cohort study of 4,349 HCV-infected patients in Denmark, computing standardized incidence ratios (SIR) of cancer incidence in HCV infected patients compared with cancer incidence of the general population. We calculated 5- and 10-year risks of developing cancer, stratifying our analyses based on the presence of HIV coinfection and cirrhosis. Results: We recorded an increased risk of primary liver cancer (SIR: 76.63 [95% CI: 51.69–109.40]), NHL (SIR: 1.89 [95% CI: 0.39–5.52]), and several smoking- and alcohol-related cancers in HCV infected patients without HIV coinfection. HCV-infected patients without HIV coinfection had a 6.3% (95% CI: 4.6%–8.7%) risk of developing cancer and 2.0% (95% CI: 1.1%–3.8%) risk of developing primary liver cancer within 10 years. Conclusion: We confirmed the association of HCV infection with primary liver cancer and NHL. We also observed an association between HCV infection and alcohol- and smoking-related cancers. PMID:20865115

  3. Different Effects of Tolvaptan in Patients with Idiopathic Membranous Nephropathy with Nephrotic Syndrome

    PubMed Central

    Tanaka, Atsushi; Nakamura, Tsukasa; Sato, Eiichi; Ueda, Yoshihiko; Node, Koichi

    2017-01-01

    This case report discusses the clinical indication for immunosuppressants in patients with idiopathic membranous nephropathy (IMN). Because this disease occasionally shows spontaneous remission, it is necessary to determine the predictive values for a therapeutic effect in order to provide appropriate treatment. Two distinct cases described herein illustrate the different effects of tolvaptan in responders and non-responders, according to the pre-treatment levels of AQP-2 immunostaining in the samples from renal biopsy and urinary levels of AQP-2 and osmolality, suggesting that these values may be useful predictors of response to tolvaptan in patients with nephrotic IMN. PMID:28090051

  4. Pharmacogenomic study in patients with multiple sclerosis

    PubMed Central

    Bustamante, Marta F.; Morcillo-Suárez, Carlos; Malhotra, Sunny; Rio, Jordi; Leyva, Laura; Fernández, Oscar; Zettl, Uwe K.; Killestein, Joep; Brassat, David; García-Merino, Juan Antonio; Sánchez, Antonio J.; Urcelay, Elena; Alvarez-Lafuente, Roberto; Villar, Lusia M.; Alvarez-Cermeño, Jose Carlos; Farré, Xavier; Lechner-Scott, Jeannette; Vandenbroeck, Koen; Rodríguez-Antigüedad, Alfredo; Drulovic, Jelena S.; Martinelli Boneschi, Filippo; Chan, Andrew; Oksenberg, Jorge; Navarro, Arcadi; Montalban, Xavier

    2015-01-01

    Objectives: We aimed to investigate the association between polymorphisms located in type I interferon (IFN)-induced genes, genes belonging to the toll-like receptor (TLR) pathway, and genes encoding neurotransmitter receptors and the response to IFN-β treatment in patients with multiple sclerosis (MS). Methods: In a first or screening phase of the study, 384 polymorphisms were genotyped in 830 patients with MS classified into IFN-β responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-β response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-β responders and 274 nonresponders). Results: Seven single nucleotide polymorphisms (SNPs) were selected from the screening phase for further validation: rs832032 (GABRR3; p = 0.0006), rs6597 (STUB1; p = 0.019), rs3747517 (IFIH1; p = 0.010), rs2277302 (PELI3; p = 0.017), rs10958713 (IKBKB; p = 0.003), rs2834202 (IFNAR1; p = 0.030), and rs4422395 (CXCL1; p = 0.017). None of these SNPs were significantly associated with IFN-β response when genotyped in an independent cohort of patients. Combined analysis of these SNPs in all patients with MS (N = 1,385) revealed 2 polymorphisms associated with IFN-β response: rs2277302 (PELI3; p = 0.008) and rs832032 (GABRR3; p = 0.006). Conclusions: These findings do not support an association between polymorphisms located in genes related to the type I IFN or TLR pathways or genes encoding neurotransmitter receptors and the clinical response to IFN-β. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted. PMID:26445728

  5. Removal of 2-arachidonylglycerol by direct hemoperfusion therapy with polymyxin B immobilized fibers benefits patients with septic shock.

    PubMed

    Kase, Yoichi; Obata, Toru; Okamoto, Yasuhisa; Iwai, Kenichi; Saito, Keita; Yokoyama, Keitaro; Takinami, Masanori; Tanifuji, Yasumasa

    2008-10-01

    Arachidonylethanolamide (AEA) and 2-arachidonylglycerol (2-AG) are endocannabinoids involved in septic shock, and 8-epi prostaglandin F2alpha (F2-isoprostane) is a biomarker of oxidative stress in biological systems. Because the antibiotic polymyxin B absorbs endocannabinoids as well as endotoxins, direct hemoperfusion therapy with polymyxin B-immobilized fibers (PMX-DHP) decreases serum levels of endocannabinoids. To investigate the features of sepsis and determine the proper use of PMX-DHP, we measured the changes in levels of endocannabinoids and F2-isoprostane in patients with septic shock. Twenty-six patients with septic shock, including those with septic shock induced by peritonitis, underwent laparotomy for drainage. Endocannabinoids absorption with PMX-DHP was examined in two groups of patients: patients whose mean arterial blood pressure (mABP) had increased more than 20 mm Hg (responder group; N = 13); and patients iwhose mABP did not increase or had increased no more than 20 mm Hg (non-responder group; N = 13). Levels of AEA did not change after PMX-DHP in either the non-responder or responder groups, whereas levels of 2-AG decreased significantly after PMX-DHP in the responder group, but not in the non-responder group. F2-isoprostane gradually increased after PMX-DHP treatment; on the other hand, levels of F2-isoprostane remained constant in the responder group. Patients with septic shock are under considerable oxidative stress, and 2-AG plays an important role in the cardiovascular status of these patients. The removal of 2-AG by PMX-DHP benefits patients with septic shock by stabilizing cardiovascular status and decreasing long-term oxidative stress.

  6. Leishmania-HIV co-infection: clinical presentation and outcomes in an urban area in Brazil.

    PubMed

    Cota, Gláucia F; de Sousa, Marcos R; de Mendonça, Andrea Laender Pessoa; Patrocinio, Allan; Assunção, Luiza Siqueira; de Faria, Sidnei Rodrigues; Rabello, Ana

    2014-04-01

    Visceral leishmaniasis (VL) is an emerging condition affecting HIV-infected patients living in Latin America, particularly in Brazil. Leishmania-HIV coinfection represents a challenging diagnosis because the clinical picture of VL is similar to that of other disseminated opportunistic diseases. Additionally, coinfection is related to treatment failure, relapse and high mortality. To assess the clinical-laboratory profile and outcomes of VL-HIV-coinfected patients using a group of non HIV-infected patients diagnosed with VL during the same period as a comparator. The study was conducted at a reference center for infectious diseases in Brazil. All patients with suspected VL were evaluated in an ongoing cohort study. Confirmed cases were divided into two groups: with and without HIV coinfection. Patients were treated according to the current guidelines of the Ministry of Health of Brazil, which considers antimony as the first-choice therapy for non HIV-infected patients and recommends amphotericin B for HIV-infected patients. After treatment, all patients with CD4 counts below 350 cells/mm3 received secondary prophylaxis with amphotericin B. Between 2011 and 2013, 168 patients with suspected VL were evaluated, of whom 90 were confirmed to have VL. In total, 51% were HIV coinfected patients (46 patients). HIV-infected patients had a lower rate of fever and splenomegaly compared with immunocompetent patients. The VL relapse rate in 6 months was 37% among HIV-infected patients, despite receiving secondary prophylaxis. The overall case-fatality rate was 6.6% (4 deaths in the HIV-infected group versus 2 deaths in the non HIV-infected group). The main risk factors for a poor outcome at 6 months after the end of treatment were HIV infection, bleeding and a previous VL episode. Although VL mortality rates among HIV-infected individuals are close to those observed among immunocompetent patients treated with amphotericin B, HIV coinfection is related to a low clinical response

  7. Leishmania-HIV Co-infection: Clinical Presentation and Outcomes in an Urban Area in Brazil

    PubMed Central

    Cota, Gláucia F.; de Sousa, Marcos R.; de Mendonça, Andrea Laender Pessoa; Patrocinio, Allan; Assunção, Luiza Siqueira; de Faria, Sidnei Rodrigues; Rabello, Ana

    2014-01-01

    Background Visceral leishmaniasis (VL) is an emerging condition affecting HIV-infected patients living in Latin America, particularly in Brazil. Leishmania-HIV coinfection represents a challenging diagnosis because the clinical picture of VL is similar to that of other disseminated opportunistic diseases. Additionally, coinfection is related to treatment failure, relapse and high mortality. Objective To assess the clinical-laboratory profile and outcomes of VL-HIV-coinfected patients using a group of non HIV-infected patients diagnosed with VL during the same period as a comparator. Methods The study was conducted at a reference center for infectious diseases in Brazil. All patients with suspected VL were evaluated in an ongoing cohort study. Confirmed cases were divided into two groups: with and without HIV coinfection. Patients were treated according to the current guidelines of the Ministry of Health of Brazil, which considers antimony as the first-choice therapy for non HIV-infected patients and recommends amphotericin B for HIV-infected patients. After treatment, all patients with CD4 counts below 350 cells/mm3 received secondary prophylaxis with amphotericin B. Results Between 2011 and 2013, 168 patients with suspected VL were evaluated, of whom 90 were confirmed to have VL. In total, 51% were HIV coinfected patients (46 patients). HIV-infected patients had a lower rate of fever and splenomegaly compared with immunocompetent patients. The VL relapse rate in 6 months was 37% among HIV-infected patients, despite receiving secondary prophylaxis. The overall case-fatality rate was 6.6% (4 deaths in the HIV-infected group versus 2 deaths in the non HIV-infected group). The main risk factors for a poor outcome at 6 months after the end of treatment were HIV infection, bleeding and a previous VL episode. Conclusion Although VL mortality rates among HIV-infected individuals are close to those observed among immunocompetent patients treated with amphotericin B, HIV

  8. Long-term effects of hypnotherapy in patients with refractory irritable bowel syndrome.

    PubMed

    Lindfors, Perjohan; Unge, Peter; Nyhlin, Henry; Ljótsson, Brjánn; Björnsson, Einar S; Abrahamsson, Hasse; Simrén, Magnus

    2012-04-01

    Gut-directed hypnotherapy is considered to be an effective treatment in irritable bowel syndrome (IBS) but few studies report the long-term effects. This retrospective study aims to evaluate the long-term perceived efficacy of gut-directed hypnotherapy given outside highly specialized hypnotherapy centers. 208 patients, who all had received gut-directed hypnotherapy, were retrospectively evaluated. The Subjective Assessment Questionnaire (SAQ) was used to measure changes in IBS symptoms, and patients were classified as responders and non-responders. Patients were also asked to report changes in health-care seeking, use of drugs for IBS symptoms, use of alternative non-pharmacological treatments, and if they still actively used hypnotherapy. Immediately after hypnotherapy, 103 of 208 patients (49%) were responders and 75 of these (73%) had improved further at the follow-up 2-7 years after hypnotherapy (mean 4 years). A majority of the responders still used hypnotherapy on a regular basis at follow-up (73%), and the responders reported a greater reduction in health-care seeking than non-responders. A total of 87% of all patients reported that they considered gut-directed hypnotherapy to be worthwhile, and this differed between responders and non-responders (100% vs. 74%; p < 0.0001). This long-term follow-up study indicates that gut-directed hypnotherapy in refractory IBS is an effective treatment option with long-lasting effects, also when given outside highly specialized hypnotherapy centers. Apart from the clinical benefits, the reduction in health-care utilization has the potential to reduce the health-care costs.

  9. Urinary nerve growth factor and a variable solifenacin dosage in patients with an overactive bladder.

    PubMed

    Ciftci, Seyfettin; Ozkurkcugil, Cuneyd; Yilmaz, Hasan; Ustuner, Murat; Yavuz, Ufuk; Yuksekkaya, Mustafa; Cekmen, Mustafa Baki

    2016-02-01

    We evaluated changes in urinary nerve growth factor (NGF) and NGF/creatinine (NGF/Cr) levels after increasing the dosage of solifenacin in overactive bladder patients. The study groups included 59 overactive bladder (OAB) patients and 20 healthy subjects as controls. We measured NGF at baseline for the patients and controls, and used the Overactive Bladder Awareness Tool (OAB-V8) to evaluate urinary symptoms. All patients received a treatment of solifenacin 5 mg for 6 weeks. The responders to treatment served as group 1 and nonresponders received solifenacin 10 mg for an additional 6 weeks. Responders and nonresponders to the 10-mg treatment were defined as groups 2 and 3 respectively. NGF was measured after each treatment using the ELISA method and normalized by the urinary creatinine levels (NGF/Cr). There were 21, 22 and 16 patients in groups 1, 2, and 3 respectively. At baseline, the NGF and NGF/Cr levels were higher in groups 1, 2, and 3 compared with the controls. After the solifenacin 5 mg treatment, the NGF and NGF/Cr levels of group 1 individuals decreased to those of the control level. After increasing the dosage of solifenacin to 10 mg in group 2, the NGF and NGF/Cr levels decreased to normal levels. In group 3 (patients who did not responded to any treatment), these levels remained unchanged. Our results suggest that urinary NGF could be a potential biomarker for monitoring the treatment of symptoms in OAB patients who are treated with solifenacin.

  10. IL2/IL21 region polymorphism influences response to rituximab in systemic lupus erythematosus patients.

    PubMed

    Márquez, Ana; Dávila-Fajardo, Cristina Lucía; Robledo, Gema; Rubio, José Luis Callejas; de Ramón Garrido, Enrique; García-Hernández, Francisco J; González-León, Rocío; Ríos-Fernández, Raquel; Barrera, José Cabeza; González-Escribano, Ma Francisca; García, Ma Teresa Camps; Palma, Ma Jesús Castillo; del Mar Ayala, Ma; Ortego-Centeno, Norberto; Martín, Javier

    2013-08-01

    To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2-IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56%) and non-responder (45.45%) SLE patients (p=0.010, odds ratio (OR)=6.10 [1.28-29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p=0.024, OR=3.53 [1.06-11.64]). Our results show for a first time that IL2-IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.

  11. Mutations of KRAS/NRAS/BRAF predict cetuximab resistance in metastatic colorectal cancer patients

    PubMed Central

    Hsu, Hung-Chih; Thiam, Tan Kien; Lu, Yen-Jung; Yeh, Chien Yuh; Tsai, Wen-Sy; You, Jeng Fu; Hung, Hsin Yuan; Tsai, Chi-Neu; Hsu, An; Chen, Hua-Chien; Chen, Shu-Jen; Yang, Tsai-Sheng

    2016-01-01

    Approximately 45% of metastatic colorectal cancer (mCRC) patients with wild-type KRAS exon 2 are resistant to cetuximab treatment. We set out to identify additional genetic markers that might predict the response to cetuximab treatment. Fifty-three wild-type KRAS exon 2 mCRC patients were treated with cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. The mutational statuses of 10 EGFR pathway genes were analyzed in primary tumors using next-generation sequencing. BRAF, PIK3CA, KRAS (exons 3 and 4), NRAS, PTEN, and AKT1 mutations were detected in 6, 6, 5, 4, 1, and 1 patient, respectively. Four of the BRAF mutations were non-V600 variants. Four tumors harbored multiple co-existing (complex) mutations. All patients with BRAF mutations or complex mutation patterns were cetuximab non-responders. All patients but one harboring KRAS, NRAS, or BRAF mutations were non-responders. Mutations in any one of these three genes were associated with a poor response rate (7.1%) and reduced survival (PFS = 8.0 months) compared to wild-type patients (74.4% and 11.6 months). Our data suggest that KRAS, NRAS, and BRAF mutations predict response to cetuximab treatment in mCRC patients. PMID:26989027

  12. Factors affecting response to hepatitis B vaccine among hemodialysis patients in a large Saudi Hemodialysis Center.

    PubMed

    Al Saran, Khalid; Sabry, Alaa; Al Halawany, Zakaria; Ismail, Mahmoud

    2014-01-01

    The aim of this study is to determine the response to hepatitis B virus (HBV) vaccination in patients on hemodialysis (HD) and to identify the factors that could affect this response. This retrospective study was carried out during the period from January 2009 to December 2009 in the Prince Salman Center for Kidney Diseases (PSCKD), Riyadh, and included 144 patients (78 males and 66 females) on regular HD, all of whom received hepatitis B vacci-nation. Patients were divided into two groups according to the level of hepatitis B surface antibodies (HBsAb): Responders group (>10 IU/L) and non-responders group (<10 IU/L). The study looked at the factors that may affect the responsiveness to hepatitis B vaccination, like gender, age, co-existence of hepatitis C virus (HCV) infection, dialysis adequacy that was evaluated by urea reduction ratio (URR) and Kt/V, hemoglobin level, albumin level, protein catabolic rate (PCR), body mass index (BMI), subjective global nutritional status (SGA) and HbA1c. There were 129 patients (89.6%) in the responders group including 69 males and 60 females and 15 patients (10.4%) in the non-responders group including nine males and six females. The mean age in the responders group and the non-responders group was 50.56 ± 15.35 and 56.87 ± 12.52 years, respectively (P = 0.128). The mean value of the PCR was 1.03 ± 0.17 and 0.88 ± 0.17 g/kg/day in the responders group and non-responders group, respectively (P = 0.002). There was no statically significant difference between the two groups regarding the presence or absence of HCV infection, age, gender, diabetes mellitus, URR, Kt/V, hemoglobin level and albumin level. We report a high response rate (89%) for HBV vaccination in our HD patients. The PCR was the only factor that affected the response to HBV vaccination in these patients.

  13. The effect of unsuccessful treatment with peginterferon and ribavirin on the liver fibrosis course of HIV/HCV-coinfected patients.

    PubMed

    Collazos, Julio; Asensi, Víctor; de la Fuente, Belén; Cartón, Jose-Antonio

    2012-12-01

    The course over time of different fibrosis parameters in HIV/HCV-coinfected patients who did not suppress HCV during anti-HCV therapy, and in patients who suppressed HCV but relapsed after treatment discontinuation is unclear. A total of 248 patients were included in the study (81 non-responders, 49 relapsers, and 118 control, untreated patients). Four primary non-invasive fibrosis indices (transient elastometry, APRI, Forns, and FIB4), as well as other fibrosis parameters, were evaluated in each group at baseline, at the end of anti-HCV therapy and at the end of follow-up (median 39.35 months from baseline). Groups were comparable in baseline characteristics, except for lower fibrosis indices in the control group. In this group there was a consistent increase in all fibrosis indices over time. On the contrary, treated patients experienced certain improvements in these indices during the period of treatment and a further worsening when the treatment was stopped, to reach the pretreatment values at the end of follow-up. Relapsers had also more favorable course than non-responders in each fibrosis parameter, but the differences were small and not statistically significant. HIV/HCV-coinfected patients who undergo unsuccessful anti-HCV treatment experience some improvement in liver fibrosis as compared to untreated patients, although the differences are small. Relapsers have also a more favorable fibrosis course than non-responders, but the differences are minimal. These improvements are only limited to the treatment period. Therefore the effect of unsuccessful treatment would only represent a transitory delay in fibrosis progression.

  14. Three most common nonsynonymous UGT1A6*2 polymorphisms (Thr181Ala, Arg184Ser and Ser7Ala) and therapeutic response to deferiprone in β-thalassemia major patients.

    PubMed

    Dadheech, Sneha; Rao, A Venkateswara; Shaheen, Uzma; Hussien, Mohammed Dyia; Jain, Suman; Jyothy, A; Munshi, Anjana

    2013-12-01

    Deferiprone is used as a chelation agent in chronic iron overload in β-thalassemia patients. Patients on deferiprone therapy show variable response to this drug in terms of reduction in iron overload as well as adverse drug reactions (ADRs). The pharmacogenetic studies on deferiprone have not carried out in patients with blood disorders in India. Therefore, the present study was carried out to evaluate the three most common nonsynonymous UGT1A6 polymorphisms Thr181Ala (541 A/G), Arg184Ser (552 A/C) and Ser7Ala (19 T/G) and therapeutic response to deferiprone in β-thalassemia major patients. Two hundred and eighty six (286) β-thalassemia major patients were involved in the study. Serum ferritin levels were estimated periodically to assess the status of the iron overload and the patients were grouped into responders and non-responders depending on the ferritin levels. The UGT1A6 2 polymorphisms were detected by PCR-RFLP methods. The association between the genotypes and outcome as well as ADRs was evaluated by Open EPI software. A significant difference was observed in the genotypic distribution of UGT1A6 2 Thr181Ala polymorphism in responders and non-responders. However, there was no difference in the genotypic distribution between patients with and without ADRs. As far as the UGT1A6 2 Arg184Ser polymorphism is concerned, no significant difference was observed between responders and non-responders. Further, evaluating the association of UGT1A6 2 Ser7Ala polymorphism with drug response, there was no significant difference in the genotypic distribution between responders and non-responders. However, there was a significant difference between responders with and without ADRs and non-responders with and without ADRs. In addition to this haplotype analysis was also carried out. However, we did not find any specific haplotype to be significantly associated with the deferiprone response in β-thalassemia major patients. © 2013 Elsevier B.V. All rights reserved.

  15. Efficacy of exogenous oral zinc in treatment of patients with carbonic anhydrase VI deficiency.

    PubMed

    Henkin, R I; Martin, B M; Agarwal, R P

    1999-12-01

    We previously described a disorder in 18 patients with decreased parotid saliva gustin/carbonic anhydrase (CA) VI secretion associated with loss of taste (hypogeusia) and smell (hyposmia) and distorted taste (dysgeusia) and smell (dysosmia). Because gustin/CAVI is a zinc-dependent enzyme we instituted a study of treatment with exogenous zinc to attempt to stimulate synthesis/secretion of gustin/CAVI and thereby attempt to correct the symptoms of this disorder. Fourteen of the 18 patients with this disorder completed the study. They were treated with 100 mg of exogenous zinc daily for 4 to 6 months, in an open clinical trial. Both before and after treatment, measurements were obtained of parotid saliva gustin/CAVI, parotid saliva, serum and urine zinc, taste and smell function, and, in some patients, examination of circumvallate taste buds by electron microscopy. Treatment success was predicated upon significant increases in parotid saliva gustin/CAVI. This occurred in 10 of the 14 patients who were labeled responders; they also exhibited improvement in taste and smell acuity, a diminution in dysgeusia and dysosmia and increased zinc concentrations in parotid saliva, serum, and urine. Taste bud morphology returned to normal in each responder in whom it was measured. No increase in gustin/CAVI occurred in 4 patients who were labeled nonresponders; they exhibited no improvement in taste or smell acuity and no increases in parotid saliva zinc. However, serum and urine zinc increased to levels similar to those measured in the 10 responders. Two of 4 nonresponders reported diminution in dysgeusia and dysosmia. Taste bud morphology did not change from the abnormal state in the 1 nonresponder in whom it was measured. Zinc treatment is effective in patients in whom this trace metal increases synthesis/secretion of gustin/CAVI and ineffective in those in whom it does not. Increased gustin/CAVI in this disorder is probably associated with zinc stimulation of the gene

  16. Syphilis in Men Who Have Sex With Men: A Warning Sign for HIV Infection.

    PubMed

    Gállego-Lezáun, C; Arrizabalaga Asenjo, M; González-Moreno, J; Ferullo, I; Teslev, A; Fernández-Vaca, V; Payeras Cifre, A

    2015-11-01

    To describe the clinical and epidemiological characteristics of syphilis in men who have sex with men (MSM) in an area of Mallorca, Spain. We performed a retrospective analysis of syphilis cases in MSM seen at a hospital in Mallorca between January 2005 and June 2013. Fifty-five cases of syphilis were recorded in MSM during the study period (34.3% of all cases diagnosed), and 74.5% of these patients had human immunodeficiency virus (HIV) coinfection. The two diseases had been diagnosed simultaneously in 70.7% of this population. Patients with HIV coinfection had a median CD4 count of 456cells/μL (range, 29-979 cells/μL). Syphilis was diagnosed clinically in 49.1% of cases and by screening in the remaining 50.9%. The most common form of syphilis was late latent or indeterminate syphilis (41.9% of cases). In the group of men with syphilis, MSM had a higher risk of HIV infection. A majority of MSM with syphilis had HIV coinfection. HIV screening is therefore essential in this population and could even result in early diagnosis. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

  17. [Effects of inhaled aerosolized iloprost in adult patients with pulmonary arterial hypertension on right heart functions].

    PubMed

    Guo, Xiao-xiao; Tian, Zhuang; Liu, Yong-tai; Wang, Qian; Li, Meng-tao; Zeng, Xiao-feng; Zhu, Wen-ling; Fang, Quan

    2011-11-01

    To explore the immediate effects of inhaled aerosolized iloprost on right heart function in adult patients with pulmonary arterial hypertension (PAH). A total of 30 PAH patients were recruited. Right heart catheterization and echocardiography were performed before and immediately after the inhalation of iloprost (20 µg). After inhalation, the values of mean pulmonary artery pressure (PAPm) and pulmonary vascular resistances (PVR) decreased markedly (42.5 ± 9.6 to 34.4 ± 11.9 mm Hg, P < 0.001; 9.6 ± 5.7 Wood unit to 7.1 ± 4.8 Wood unit, P < 0.001). And the value of tricuspid annular systolic motion peak velocity (TASm) increased markedly [(10.7 ± 2.1) cm/s vs (11.9 ± 2.5) cm/s, P < 0.01]. The baseline level of TASm was higher in acute responders than non-responders [(12.0 ± 2.2) cm/s vs (10.1 ± 1.8) cm/s, P = 0.01] and TASm increased markedly after inhalation in non-responders [(10.1 ± 1.8) cm/s vs (11.6 ± 2.3) cm/s, P < 0.01]. The inhalation of iloprost decreases the levels of PAPm and PVR and improve right heart functions in adult PAH patients. For non-responders, right heart function is worse and more benefits may be achieved after the inhalation of iloprost.

  18. Symptom predictors of response to electroconvulsive therapy in older patients with treatment-resistant depression

    PubMed Central

    Tominaga, Keiichiro; Okazaki, Mioto; Higuchi, Hisashi; Utagawa, Itaru; Nakamura, Etsuko; Yamaguchi, Noboru

    2011-01-01

    Background: Electroconvulsive therapy (ECT) has been used for treatment-resistant depression. However, predictors of response to ECT have not been adequately studied using the Montgomery and Åsberg Depression Rating Scale, especially in older patients with treatment-resistant depression. Methods: This study included 18 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision criteria for a diagnosis of major depressive disorder or bipolar disorder with a current major depressive episode, and met the definition of treatment-resistant depression outlined by Thase and Rush, scoring ≥21 on the Montgomery and Åsberg Depression Rating Scale. The three-factor model of the Montgomery and Åsberg Depression Rating Scale was used for analysis. Factor 1 was defined by three items, factor 2 by four items, and factor 3 by three items, representing dysphoria, retardation, and vegetative symptoms, respectively. ECT was performed twice a week for a total of six sessions using a Thymatron System IV device with the brief pulse technique. Clinical responses were defined on the basis of a ≥50% decrease in total pretreatment Montgomery and Åsberg Depression Rating Scale scores. Results: The mean pretreatment factor 2 score for responders (n = 7) was significantly lower than that for nonresponders (n = 11). Furthermore, a significant difference in mean factor 3 score between responders and nonresponders was observed one week after six sessions of ECT, indicating a time lag of response. No significant differences were observed for age, number of previous episodes, and duration of the current episode between responders and nonresponders. Conclusion: This study suggests that a low pretreatment factor 2 score is a good predictor of response to ECT in older patients with major depression. PMID:21845058

  19. [Interferon-alpha and liver fibrosis in patients with chronic damage due to hepatitis C virus].

    PubMed

    Gonzalez-Huezo, María Sarai; Gallegos-Orozco, Juan Fernando

    2003-01-01

    The present review focuses on the published information published regarding the effects of interferon alpha therapy on liver fibrosis in patients with chronic liver damage secondary to hepatitis C infection. Data reviewed included results of the in vitro effects of interferon on hepatic cell line cultures with regards to indirect markers of fibrosis, activation of hepatic stellate cells and oxidative stress response. In the clinical arena, there is current clear evidence of a favorable histological outcome in patients with sustained viral response to interferon therapy. For this reason, the current review focuses more on the histological outcomes regarding liver fibrosis in patients who have not attained viral response to therapy (non-responders) or who already have biopsy defined cirrhosis. Data in these patients were analyzed according to the results of objective testing of fibrosis through the assessment of liver biopsy and its change during time, specially because the morbidity and mortality of this disease is directly related to the complications of liver cirrhosis and not necessarily to the persistence of the hepatitis C virus. Lastly, it is concluded that the process of liver fibrosis/cirrhosis is a dynamic one and that there is some evidence to support the usefulness of interferon alpha therapy as a means to halt or retard the progression of hepatic fibrosis. The result of current clinical trials in which interferon therapy is being used to modify the progression of fibrosis in non-responders or cirrhotic patients is eagerly awaited.

  20. Clinical profile and treatment outcome of older (>75 years) patients with systemic AL amyloidosis

    PubMed Central

    Sachchithanantham, Sajitha; Offer, Mark; Venner, Christopher; Mahmood, Shameem A.; Foard, Darren; Rannigan, Lisa; Lane, Thirusha; Gillmore, Julian D.; Lachmann, Helen J.; Hawkins, Philip N.; Wechalekar, Ashutosh D.

    2015-01-01

    Systemic AL amyloidosis, a disease with improving outcomes using novel therapies, is increasingly recognized in the elderly but treatment and outcomes have not been systematically studied in this group of patients in whom comorbidities and frailty may compound morbidity and mortality. We report the outcomes of 295 patients with systemic AL amyloidosis ≥75 years seen at the UK National Amyloidosis Centre from 2005–2012. The median age was 78.5 years. The median overall survival was 20 months. Two hundred and thirty-eight patients received chemotherapy and 57 elected for supportive care only (overall survival – 24 and 8.4 months, respectively). On intention-to-treat analysis, 44% achieved a hematologic response including a very good partial response or better in 23%. The median overall survival was 6.2 years in patients achieving very good partial response or better at the 6-month landmark analysis and 1.5 years in non-responders. Factors independently indicating a poor prognosis were: cardiac involvement, performance status ≥2; systolic blood pressure <100 mmHg and, on landmark analysis, achieving less than a very good partial response. Treatment of systemic AL amyloidosis in the elderly is challenging. Deep clonal responses are associated with excellent survival and organ responses. Achieving a response to the first-line regimen appears particularly important as outcomes of non-responders are similar to those of untreated patients. Prospective trials with lower toxicity, outpatient treatment regimens are needed. PMID:26294730

  1. Inflammatory and Antioxidant Pattern Unbalance in “Clopidogrel-Resistant” Patients during Acute Coronary Syndrome

    PubMed Central

    Gori, Anna Maria; Cecchettini, Antonella; Parodi, Guido; Marcucci, Rossella; Parolini, Marina; Romagnuolo, Ilaria; Citti, Lorenzo; Abbate, Rosanna

    2015-01-01

    Background. In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel. Material and Methods. Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined. Results. Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNγ, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased. Conclusions. In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness. PMID:25873769

  2. Predictors of response to therapy with omalizumab in patients with severe allergic asthma - a real life study.

    PubMed

    Kallieri, Maria; Papaioannou, Andriana I; Papathanasiou, Evgenia; Ntontsi, Polyxeni; Papiris, Spyridon; Loukides, Stelios

    2017-08-01

    Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab. We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician's global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders. Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV1 and FEV1/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV1 (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709). Lower baseline FEV1 and higher IL-13 levels in induced sputum supernatant were predictors of response to

  3. Normalization of compression-induced hemodynamics in patients responding to neoadjuvant chemotherapy monitored by dynamic tomographic optical breast imaging (DTOBI)

    PubMed Central

    Sajjadi, Amir Y.; Isakoff, Steven J.; Deng, Bin; Singh, Bhawana; Wanyo, Christy M.; Fang, Qianqian; Specht, Michelle C.; Schapira, Lidia; Moy, Beverly; Bardia, Aditya; Boas, David A.; Carp, Stefan A.

    2017-01-01

    We characterize novel breast cancer imaging biomarkers for monitoring neoadjuvant chemotherapy (NACT) and predicting outcome. Specifically, we recruited 30 patients for a pilot study in which NACT patients were imaged using dynamic tomographic optical breast imaging (DTOBI) to quantify the hemodynamic changes due to partial mammographic compression. DTOBI scans were obtained pre-treatment (referred to as day 0), as well as 7 and 30 days into therapy on female patients undergoing NACT. We present data for the 13 patients who participated in both day 0 and 7 measurements and had evaluable data, of which 7 also returned for day 30 measurements. We acquired optical images over 2 minutes following 4-8 lbs (18-36 N) of compression. The timecourses of tissue-volume averaged total hemoglobin (HbT), as well as hemoglobin oxygen saturation (SO2) in the tumor vs. surrounding tissues were compared. Outcome prediction metrics based on the differential behavior in tumor vs. normal areas for responders (>50% reduction in maximum diameter) vs. non-responders were analyzed for statistical significance. At baseline, all patients exhibit an initial decrease followed by delayed recovery in HbT, and SO2 in the tumor area, in contrast to almost immediate recovery in surrounding tissue. At day 7 and 30, this contrast is maintained in non-responders; however, in responders, the contrast in hemodynamic time-courses between tumor and normal tissue starts decreasing at day 7 and substantially disappears at day 30. At day 30 into NACT, responding tumors demonstrate “normalization” of compression induced hemodynamics vs. surrounding normal tissue whereas non-responding tumors did not. This data suggests that DTOBI imaging biomarkers, which are governed by the interplay between tissue biomechanics and oxygen metabolism, may be suitable for guiding NACT by offering early predictions of treatment outcome. PMID:28270967

  4. Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs.

    PubMed

    Bennet, Sean M P; Böhn, Lena; Störsrud, Stine; Liljebo, Therese; Collin, Lena; Lindfors, Perjohan; Törnblom, Hans; Öhman, Lena; Simrén, Magnus

    2017-04-17

    The effects of dietary interventions on gut bacteria are ambiguous. Following a previous intervention study, we aimed to determine how differing diets impact gut bacteria and if bacterial profiles predict intervention response. Sixty-seven patients with IBS were randomised to traditional IBS (n=34) or low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) (n=33) diets for 4 weeks. Food intake was recorded for 4 days during screening and intervention. Faecal samples and IBS Symptom Severity Score (IBS-SSS) reports were collected before (baseline) and after intervention. A faecal microbiota dysbiosis test (GA-map Dysbiosis Test) evaluated bacterial composition. Per protocol analysis was performed on 61 patients from whom microbiome data were available. Responders (reduced IBS-SSS by ≥50) to low FODMAP, but not traditional, dietary intervention were discriminated from non-responders before and after intervention based on faecal bacterial profiles. Bacterial abundance tended to be higher in non-responders to a low FODMAP diet compared with responders before and after intervention. A low FODMAP intervention was associated with an increase in Dysbiosis Index (DI) scores in 42% of patients; while decreased DI scores were recorded in 33% of patients following a traditional IBS diet. Non-responders to a low FODMAP diet, but not a traditional IBS diet had higher DI scores than responders at baseline. Finally, while a traditional IBS diet was not associated with significant reduction of investigated bacteria, a low FODMAP diet was associated with reduced Bifidobacterium and Actinobacteria in patients, correlating with lactose consumption. A low FODMAP, but not a traditional IBS diet may have significant impact on faecal bacteria. Responsiveness to a low FODMAP diet intervention may be predicted by faecal bacterial profiles. NCT02107625. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  5. Changes of central venous oxygen saturation define fluid responsiveness in patients with septic shock: A prospective observational study.

    PubMed

    Xu, Biao; Yang, Xiaobo; Wang, Chunyao; Jiang, Wei; Weng, Li; Hu, Xiaoyun; Peng, Jinmin; Du, Bin

    2017-04-01

    To evaluate whether the changes of central venous oxygen saturation (Scvo2) after fluid challenge can define fluid responsiveness in patients with septic shock. In this prospective observational study, septic shock patients with invasive cardiac output monitoring requiring fluid challenge were included. Cardiac index (CI) and Scvo2 were measured before and after fluid challenges. The changes of CI (ΔCI) and the changes of Scvo2 (ΔScvo2) were calculated and analyzed using Pearson correlation. Receiver operating characteristics curve (ROC) analysis was used to classify fluid responders and nonresponders. Area under ROC was calculated. Forty patients were included and 18 patients (45%) were fluid responders. In the responders, CI increased from 3.4±1.1 to 4.4±1.0 L min(-1) m(-2) and Scvo2 from 69.6%±9.8% to 77.1%±8.9% (both P<.001) after fluid challenge. In the nonresponders, neither CI nor Scvo2 changed (4.1±1.3 vs 4.1±1.3 L min(-1) m(-2), 71.0%±13.8% vs 70.6%±14.1%, both P>.05). The correlation between ΔScvo2 and ΔCI was significant (r=0.702, P<.001). The area under ROC of ΔScvo2 to define fluid responsiveness was 0.88 (95% confidence interval [95% CI], 0.76-0.99). A ΔScvo2 threshold value of 5.0% discriminated responders from nonresponders with sensitivity of 0.78 (95% CI, 0.52-0.93) and specificity of 0.95 (95% CI, 0.75-1.00). The changes of Scvo2 correlate with the changes of CI, and the changes of Scvo2 define fluid responsiveness in patients with septic shock. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Association between baseline impedance values and response proton pump inhibitors in patients with heartburn.

    PubMed

    de Bortoli, Nicola; Martinucci, Irene; Savarino, Edoardo; Tutuian, Radu; Frazzoni, Marzio; Piaggi, Paolo; Bertani, Lorenzo; Furnari, Manuele; Franchi, Riccardo; Russo, Salvatore; Bellini, Massimo; Savarino, Vincenzo; Marchi, Santino

    2015-06-01

    Esophageal impedance measurements have been proposed to indicate the status of the esophageal mucosa, and might be used to study the roles of the impaired mucosal integrity and increased acid sensitivity in patients with heartburn. We compared baseline impedance levels among patients with heartburn who did and did not respond to proton pump inhibitor (PPI) therapy, along with the pathophysiological characteristics of functional heartburn (FH). In a case-control study, we collected data from January to December 2013 on patients with heartburn and normal findings from endoscopy who were not receiving PPI therapy and underwent impedance pH testing at hospitals in Italy. Patients with negative test results were placed on an 8-week course of PPI therapy (84 patients received esomeprazole and 36 patients received pantoprazole). Patients with more than 50% symptom improvement were classified as FH/PPI responders and patients with less than 50% symptom improvement were classified as FH/PPI nonresponders. Patients with hypersensitive esophagus and healthy volunteers served as controls. In all patients and controls, we measured acid exposure time, number of reflux events, baseline impedance, and swallow-induced peristaltic wave indices. FH/PPI responders had higher acid exposure times, numbers of reflux events, and acid refluxes compared with FH/PPI nonresponders (P < .05). Patients with hypersensitive esophagus had mean acid exposure times and numbers of reflux events similar to those of FH/PPI responders. Baseline impedance levels were lower in FH/PPI responders and patients with hypersensitive esophagus, compared with FH/PPI nonresponders and healthy volunteers (P < .001). Swallow-induced peristaltic wave indices were similar between FH/PPI responders and patients with hypersensitive esophagus. Patients with FH who respond to PPI therapy have impedance pH features similar to those of patients with hypersensitive esophagus. Baseline impedance measurements might allow for

  7. Treatment of early non-response in patients with schizophrenia: assessing the efficacy of antipsychotic dose escalation.

    PubMed

    Loebel, Antony; Citrome, Leslie; Correll, Christoph U; Xu, Jane; Cucchiaro, Josephine; Kane, John M

    2015-10-31

    Early non-response to antipsychotic treatment in patients with schizophrenia has been shown in multiple studies to predict poor response at short-term trial endpoint. Therefore, strategies to address the challenge of non-improvement early in the course of treatment are needed. A novel trial design was developed to assess the potential utility of antipsychotic dose escalation in patients with an inadequate initial treatment response. This design was embedded in a study intended to assess the efficacy of low dose lurasidone in patients with schizophrenia. The purpose of this report is to describe the background, rationale and design of this study that included a novel method for the assessment of the potential for dose-response in early non-responding patients with schizophrenia. In this 6-week, international, multicenter, double-blind trial, eligible adults with acute schizophrenia were randomized to receive fixed doses of lurasidone 20 mg/day, 80 mg/day (active control), or placebo in a 1:2:1 ratio. Patients initially randomized to lurasidone 80 mg/day who did not have a Positive and Negative Syndrome Scale total score improvement ≥ 20% at Week 2 were re-randomized on a 1:1 basis to receive either lurasidone 80 mg/day or lurasidone 160 mg/day for the remainder of the trial. All other groups remained on their initially assigned treatment. The formal primary objective of the study was to evaluate the efficacy of low-dose lurasidone (20 mg/day) compared to placebo; secondary objectives included evaluating the efficacy of lurasidone 80 mg/day versus 160 mg/day in early non-responders, and evaluating the efficacy of lurasidone in all subjects initially randomized to 80 mg/day versus placebo. Since a lack of early improvement predicts poor response to short-term antipsychotic treatment in patients with schizophrenia, several treatment strategies have been proposed to enhance treatment outcome in early non-responders. A novel clinical trial design involving a placebo

  8. Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus.

    PubMed

    Kansal, Amit; Tripathi, Deepak; Rai, Mohit K; Agarwal, Vikas

    2016-02-01

    Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.

  9. Clinical predictive circulating peptides in rectal cancer patients treated with neoadjuvant chemoradiotherapy.

    PubMed

    Crotti, Sara; Enzo, Maria Vittoria; Bedin, Chiara; Pucciarelli, Salvatore; Maretto, Isacco; Del Bianco, Paola; Traldi, Pietro; Tasciotti, Ennio; Ferrari, Mauro; Rizzolio, Flavio; Toffoli, Giuseppe; Giordano, Antonio; Nitti, Donato; Agostini, Marco

    2015-08-01

    Preoperative chemoradiotherapy is worldwide accepted as a standard treatment for locally advanced rectal cancer. Current standard of treatment includes administration of ionizing radiation for 45-50.4 Gy in 25-28 fractions associated with 5-fluorouracil administration during radiation therapy. Unfortunately, 40% of patients have a poor or absent response and novel predictive biomarkers are demanding. For the first time, we apply a novel peptidomic methodology and analysis in rectal cancer patients treated with preoperative chemoradiotherapy. Circulating peptides (Molecular Weight <3 kDa) have been harvested from patients' plasma (n = 33) using nanoporous silica chip and analyzed by Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometer. Peptides fingerprint has been compared between responders and non-responders. Random Forest classification selected three peptides at m/z 1082.552, 1098.537, and 1104.538 that were able to correctly discriminate between responders (n = 16) and non-responders (n = 17) before therapy (T0) providing an overall accuracy of 86% and an area under the receiver operating characteristic (ROC) curve of 0.92. In conclusion, the nanoporous silica chip coupled to mass spectrometry method was found to be a realistic method for plasma-based peptide analysis and we provide the first list of predictive circulating biomarker peptides in rectal cancer patients underwent preoperative chemoradiotherapy.

  10. Evaluations of primary lesions by endoscopy clearly distinguishes prognosis in patients with gastric cancer who receive chemotherapy

    PubMed Central

    Shibata, Tomoyuki; Okubo, Masaaki; Kawamura, Tomohiko; Horiguchi, Noriyuki; Yoshida, Dai; Ishizuka, Takamitsu; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Ohmiya, Naoki

    2017-01-01

    Background Chemotherapy may improve outcomes in gastric cancer (GC), especially for the patients with advanced stage. To explore useful predictive factor for GC performing chemotherapy, we compared the tumor responses assessed using computed tomography (CT) with endoscopy based criteria. Methods 192 GC patients performing chemotherapy were retrospectively studied. CT based response assessment was performed after 2 courses of treatment. Endoscopic evaluation according to The Japanese classification of gastric carcinoma was also performed at same period. Data were correlated with overall survival (OS) and progression-free survival (PFS). Results Majority of the cases (n = 178, 93%) received S-1 based chemotherapy as the first line treatment. 55 (29%) and 91 (47%) cases were considered to be CT and endoscopic responders. Endoscopic responder was more clearly associated with better OS and PFS compared to CT based responder by the log-rank test (P<0.0001 vs. 0.01 and P<0.0001 vs. 0.008, respectively). The association was more striking among patients performing neoadjuvant chemotherapy (P<0.0001 vs. 0.15 and P<0.0001 vs. 0.1, respectively). Multivariate survival analysis using Cox's regression model revealed that endoscopic non-responder was the independent predictive factor, being more strongly associated with worse OS when compared to CT non-responder (hazard ratio: 4.60 vs. 1.77, 95% confidence interval: 2.83–7.49 vs.1.08–2.89, P<0.0001 vs. 0.02). More advanced T, N stage and cases who had peritoneal dissemination were significantly associated with endoscopic non-responder (all P values <0.01). Conclusion Endoscopy based evaluation of primary lesions are clearly associated with prognosis in patients with GC who perform chemotherapy. PMID:28288188

  11. Amygdala Subregions Tied to SSRI and Placebo Response in Patients with Social Anxiety Disorder

    PubMed Central

    Faria, Vanda; Appel, Lieuwe; Åhs, Fredrik; Linnman, Clas; Pissiota, Anna; Frans, Örjan; Bani, Massimo; Bettica, Paolo; Pich, Emilio M; Jacobsson, Eva; Wahlstedt, Kurt; Fredrikson, Mats; Furmark, Tomas

    2012-01-01

    The amygdala is a key structure in the pathophysiology of anxiety disorders, and a putative target for anxiolytic treatments. Selective serotonin reuptake inhibitors (SSRIs) and placebo seem to induce anxiolytic effects by attenuating amygdala responsiveness. However, conflicting amygdala findings have also been reported. Moreover, the neural profile of responders and nonresponders is insufficiently characterized and it remains unknown whether SSRIs and placebo engage common or distinct amygdala subregions or different modulatory cortical areas. We examined similarities and differences in the neural response to SSRIs and placebo in patients with social anxiety disorder (SAD). Positron emission tomography (PET) with oxygen-15-labeled water was used to assess regional cerebral blood flow (rCBF) in 72 patients with SAD during an anxiogenic public speaking task, before and after 6–8 weeks of treatment under double-blind conditions. Response rate was determined by the Clinical Global Impression-Improvement scale. Conjunction analysis revealed a common rCBF-attenuation from pre- to post-treatment in responders to SSRIs and placebo in the left basomedial/basolateral and right ventrolateral amygdala. This rCBF pattern correlated with behavioral measures of reduced anxiety and differentiated responders from nonresponders. However, nonanxiolytic treatment effects were also observed in the amygdala. All subgroups, including nonresponders, showed deactivation of the left lateral part of the amygdala. No rCBF differences were found between SSRI responders and placebo responders. This study provides new insights into the brain dynamics underlying anxiety relief by demonstrating common amygdala targets for pharmacologically and psychologically induced anxiety reduction, and by showing that the amygdala is functionally heterogeneous in anxiolysis. PMID:22617357

  12. Hepatitis C virus core antigen in the management of patients treated with new direct-acting antivirals.

    PubMed

    Arboledas, Juan Carlos Alados; Guerrero, Inmaculada Pavón; Rodríguez, María José Blanco; Martos, Eva Torres; Pérez, Ana Belén; León, Cristina Cepero; Sierra Sánchez, Jesus F; Prieto, María Dolores López; Porcuna, Natalia Chueca; Mochón, María Dolores Ocete; Macías, Juan; de la Iglesia Salgado, Alberto; Granger, Javier Rodríguez; Fernández, Marcial Delgado; Lozano, Inmaculada Guerrero; Ramírez, Elena Reigadas; Rivero, Antonio; Del Carmen Lozano Domínguez, María; Viciana, Isabel; Montemayor, Juan Carlos Galán; García, Federico García

    2017-09-01

    We evaluated the utility of Architect core antigen assay® Abbott Diagnostics (HCVAg) for monitoring patients with HCV infection and compared to HCV-RNA quantification (Cobas Ampliprep TaqMan-Roche Diagnostics). Samples from 262 patients were studied. Mean baseline HCV RNA and HCVAg levels were similar for responders (6.2 log IU/mL and 3.4 log fmol/L) and non-responders (6.1 log IU/mL and 3.2 log fmol/L), respectively. Only 10 patients failed to achieve SVR12 and all were detected by both assays. To evaluate HCVAg quantification as a tool for the detection of failure to DAAs, we performed a retrospective study of 132 non-responder patients. Mean HCV RNA and HCVAg levels at the time of detection of therapeutic failure were 5.88±0.97 log IU/mL and 3.19±0.79 log fmol/L, respectively. HCVAg (>3 fmol/L) was detected in 130/132 patients (98.5%). HCVAg assay was useful for patient selection and for evaluating virological response to DAAs in the real world. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Vitamin D receptor genetic variants are associated with chemotherapy response and prognosis in patients with advanced non-small-cell lung cancer.

    PubMed

    Xiong, Liwen; Cheng, Jinsong; Gao, Jinyu; Wang, Jipeng; Liu, Xiaoning; Wang, Lixin

    2013-07-01

    The aim of this study was to explore the association between vitamin D receptor (VDR) genetic polymorphisms and platinum-based chemotherapy response as well as the prognosis of non-small-cell lung cancer (NSCLC) in a Chinese cohort. Seven hundred fifty-five patients with advanced NSCLC (stage III [A + B] or stage IV) were enrolled. Platinum-based chemotherapy was given to each patient with NSCLC, and the therapeutic effect was evaluated. The VDR polymorphisms were genotyped. Three hundred twenty-one (42.5%) patients responded to chemotherapy (complete response [CR] or partial response [PR]) and 434 (57.5%) patients were nonresponders (stable disease [SD] or progressive disease [PD]). The genotypic and allelic frequencies of FokI, BsmI, and TaqI were not significantly different between chemotherapy responders and nonresponders. However, the genotypic and allelic frequencies of ApaI thymine (T) > guanine (G) were significantly different between the responders and nonresponders. Multivariate logistic regression analysis showed that GG genotype carriers of ApaI T > G had a higher chance of being responders. The ApaI T > G polymorphisms affected mean overall survival (OS). The GG genotype carriers of ApaI polymorphisms had a longer mean OS compared with TT carriers. Multivariate Cox regression analyses showed that ApaI T > G was significantly associated with OS. We found that there was an effect of ApaI T > G polymorphisms of the VDR gene on the chemotherapy response in patients with NSCLC, as well as a prognostic role of the VDR gene polymorphisms in Chinese patients with advanced NSCLC. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C

    PubMed Central

    2010-01-01

    Background Interferon (IFN)-α receptor 1 (ifnar1) and suppressor of cytokine signaling 1 (socs1) transcription levels were quantified in peripheral blood mononuclear cells (PBMC) of 59 patients infected with hepatitis C virus (HCV) and 17 non-infected individuals. Samples were obtained from patients infected with HCV that were either untreated or treated with IFN-α2 plus ribavirin for 1 year and divided into responders and non-responders based on viral load reduction 6 months after treatment. Ifnar1 and socs1 transcription was quantified by real-time RT-PCR, and the fold difference (2-ΔΔCT) with respect to hprt housekeeping gene was calculated. Results Ifnar1 transcription increased significantly in HCV-infected patients either untreated (3.26 ± 0.31), responders (3.1 ± 0.23) and non-responders (2.18 ± 0.23) with respect to non-infected individuals (1 ± 0.34; P = 0.005). Ifnar1 transcription increased significantly (P = 0.003) in patients infected with HCV genotypes 1a (4.74 ± 0.25) and 1b (2.81 ± 0.25) but not in 1a1b (1.58 ± 0.21). No association was found of Ifnar1 transcription with disease progress, initial viral load or other clinical factors. With respect to socs1 transcription, values were similar for non-infected individuals (1 ± 0.28) and untreated patients (0.99 ± 0.41) but increased in responders (2.81 ± 0.17) and non-responder patients (1.67 ± 0.41). Difference between responder and non-responder patients was not statistically significant. Socs1 transcription increased in patients infected with HCV genotypes 1a and 1b (2.87 ± 0.45 and 2.22 ± 0.17, respectively) but not in 1a1b (1.28 ± 0.40). Socs1 transcript was absent in three patients infected with HCV genotype 1b. A weak correlation between ifnar1 and socs1 transcription was found, when Spearman's correlation coefficient was calculated. Conclusion Our results suggest that HCV infection may up-regulate ifnar1 transcription. HCV genotypes differ in their capacity to affect ifnar1 and

  15. Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C.

    PubMed

    Sedeño-Monge, Virginia; Santos-López, Gerardo; Rocha-Gracia, Rosa C; Meléndez-Mena, Daniel; Ramírez-Mata, Alberto; Vallejo-Ruiz, Verónica; Reyes-Leyva, Julio

    2010-09-18

    Interferon (IFN)-α receptor 1 (ifnar1) and suppressor of cytokine signaling 1 (socs1) transcription levels were quantified in peripheral blood mononuclear cells (PBMC) of 59 patients infected with hepatitis C virus (HCV) and 17 non-infected individuals. Samples were obtained from patients infected with HCV that were either untreated or treated with IFN-α2 plus ribavirin for 1 year and divided into responders and non-responders based on viral load reduction 6 months after treatment. Ifnar1 and socs1 transcription was quantified by real-time RT-PCR, and the fold difference (2(⁻ΔΔCT)) with respect to hprt housekeeping gene was calculated. Ifnar1 transcription increased significantly in HCV-infected patients either untreated (3.26 ± 0.31), responders (3.1 ± 0.23) and non-responders (2.18 ± 0.23) with respect to non-infected individuals (1 ± 0.34; P = 0.005). Ifnar1 transcription increased significantly (P = 0.003) in patients infected with HCV genotypes 1a (4.74 ± 0.25) and 1b (2.81 ± 0.25) but not in 1a1b (1.58 ± 0.21). No association was found of Ifnar1 transcription with disease progress, initial viral load or other clinical factors. With respect to socs1 transcription, values were similar for non-infected individuals (1 ± 0.28) and untreated patients (0.99 ± 0.41) but increased in responders (2.81 ± 0.17) and non-responder patients (1.67 ± 0.41). Difference between responder and non-responder patients was not statistically significant. Socs1 transcription increased in patients infected with HCV genotypes 1a and 1b (2.87 ± 0.45 and 2.22 ± 0.17, respectively) but not in 1a1b (1.28 ± 0.40). Socs1 transcript was absent in three patients infected with HCV genotype 1b. A weak correlation between ifnar1 and socs1 transcription was found, when Spearman's correlation coefficient was calculated. Our results suggest that HCV infection may up-regulate ifnar1 transcription. HCV genotypes differ in their capacity to affect ifnar1 and socs1 transcription, as

  16. Influence of disease manifestation and antineutrophil cytoplasmic antibody titer on the response to pulse cyclophosphamide therapy in patients with Wegener's granulomatosis.

    PubMed

    Reinhold-Keller, E; Kekow, J; Schnabel, A; Schmitt, W H; Heller, M; Beigel, A; Duncker, G; Gross, W L

    1994-06-01

    To assess the effectiveness of pulse cyclophosphamide (CYC) in the treatment of Wegener's granulomatosis (WG) and to identify the patients who are responsive to the treatment. The prospective study included 43 patients with biopsy-proven WG. Clinical, radiographic, laboratory, and immunologic data were evaluated for predictive values regarding the outcome of pulse CYC therapy. Only 42% of the patients showed complete or partial remission that lasted at least 6 months after cessation of pulse CYC therapy. These responders had a higher frequency of disease activity limited to the upper and lower respiratory tract (39%, versus 8% in the nonresponder group; P < 0.05) and had lower titers of classic antineutrophil cytoplasmic antibody (cANCA) prior to treatment (< 1:64 42%, versus 6% in the nonresponder group; P < 0.05). In the 58% of patients who did not respond to pulse CYC treatment, there was both systemic disease involving more than 4 organ systems (mainly, the heart, nervous system, eye, and skin) and constitutional symptoms. Serious side effects induced by pulse CYC occurred in only 1 patient. Based on these findings, pulse CYC therapy appears to be effective in WG patients with moderate disease activity and low titers of cANCA, but of little benefit in patients with severe WG. Pulse CYC should therefore not be used as first-line therapy in patients with severe and rapidly progressing forms of WG associated with high titers of cANCA.

  17. Response to intravenous iron in patients with iron deficiency anemia (IDA) and restless leg syndrome (Willis-Ekbom disease).

    PubMed

    Mehmood, Tahir; Auerbach, Michael; Earley, Christopher J; Allen, Richard P

    2014-12-01

    Iron deficiency anemia (IDA) engenders restless legs syndrome (RLS, aka Willis-Ekbom disease). Intravenous (IV) iron can rapidly reverse IDA and would be expected to similarly reverse RLS caused by IDA. This is the first consecutive case series evaluating the effects of IV iron therapy on RLS occurring with IDA (RLS-IDA). RLS-IDA patients were evaluated before and 7-12 months after a 1000-mg IV infusion of low-molecular-weight iron dextran (INFeD(@)) using validated questionnaires and standardized telephone interview. Patients were classified as respondent versus nonrespondent for RLS improvement. Follow-up data were obtained on 42 (70%) of 60 consecutive RLS-IDA patients. The symptoms of RLS were reduced in 76% (32/42) with 47% (20/42) showing an extended response lasting >6 months. The response did not relate to age or gender, but tended to be less among African-Americans than Whites (40% (2/5) vs. 81% (30/37), p = 0.078). White respondents versus nonrespondents had higher hemoglobin levels after treatment (12.1 vs. 11.3 g/dl, p = 0.03). RLS-IDA is reduced after administration of IV iron in most cases, but the 24% failing to respond was higher than expected. The nonrespondents all showed below-normal hemoglobin levels (<12.5 g/dl) suggesting a failure of adequate treatment of the iron deficiency. IV iron treatment of the RLS with IDA likely requires ensuring more than minimally adequate body iron stores to support iron delivery to the brain. For some, this may require a dose higher than the customary 1000-mg IV iron used for the treatment of either IDA or RLS alone. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Hepcidin-25, mean corpuscular volume, and ferritin as predictors of response to oral iron supplementation in hemodialysis patients.

    PubMed

    Takasawa, Kazuya; Takaeda, Chikako; Maeda, Teiryo; Ueda, Norishi

    2014-12-29

    The benefit of oral iron therapy (OIT) and factors predictive of OIT response are not established in hemodialysis (HD) patients with iron deficiency anemia (IDA). We examined the values of hepcidin-25, mean corpuscular volume (MCV), and ferritin as predictors of OIT response. Oral ferrous fumarate (50 mg/day, 8 weeks) was given to 51 HD patients with IDA (hemoglobin (Hb) < 12 g/dL, ferritin < 100 ng/mL) treated with an erythropoietin activator. Sixteen patients were responders (improvement of Hb (ΔHb) ≥ 2 g/dL) and 35 were non-responders (ΔHb < 2g/dL). Baseline Hb, MCV, serum hepcidin-25, ferritin, iron parameters, and C-reactive protein (CRP) before and ΔHb after OIT were compared between groups. Hepcidin-25, MCV, ferritin, and transferrin saturation were lower in the responders than in the non-responders. Hepcidin-25 positively correlated with ferritin. Hepcidin-25, MCV, and ferritin positively correlated with baseline Hb and negatively correlated with ΔHb. Despite normal CRP levels in all patients, CRP correlated positively with hepcidin-25 and ferritin. Stepwise multiple linear regression analysis and receiver operating characteristics curve analysis revealed that hepcidin-25, MCV, and ferritin could predict OIT response. We conclude that hepcidin-25, MCV, and ferritin could be useful markers of iron storage status and may help predict OIT response in HD patients.

  19. Hepcidin-25, Mean Corpuscular Volume, and Ferritin as Predictors of Response to Oral Iron Supplementation in Hemodialysis Patients

    PubMed Central

    Takasawa, Kazuya; Takaeda, Chikako; Maeda, Teiryo; Ueda, Norishi

    2014-01-01

    The benefit of oral iron therapy (OIT) and factors predictive of OIT response are not established in hemodialysis (HD) patients with iron deficiency anemia (IDA). We examined the values of hepcidin-25, mean corpuscular volume (MCV), and ferritin as predictors of OIT response. Oral ferrous fumarate (50 mg/day, 8 weeks) was given to 51 HD patients with IDA (hemoglobin (Hb) < 12 g/dL, ferritin < 100 ng/mL) treated with an erythropoietin activator. Sixteen patients were responders (improvement of Hb (ΔHb) ≥ 2 g/dL) and 35 were non-responders (ΔHb < 2g/dL). Baseline Hb, MCV, serum hepcidin-25, ferritin, iron parameters, and C-reactive protein (CRP) before and ΔHb after OIT were compared between groups. Hepcidin-25, MCV, ferritin, and transferrin saturation were lower in the responders than in the non-responders. Hepcidin-25 positively correlated with ferritin. Hepcidin-25, MCV, and ferritin positively correlated with baseline Hb and negatively correlated with ΔHb. Despite normal CRP levels in all patients, CRP correlated positively with hepcidin-25 and ferritin. Stepwise multiple linear regression analysis and receiver operating characteristics curve analysis revealed that hepcidin-25, MCV, and ferritin could predict OIT response. We conclude that hepcidin-25, MCV, and ferritin could be useful markers of iron storage status and may help predict OIT response in HD patients. PMID:25551249

  20. Association between ABCB1 (MDR1) gene 3435 C>T polymorphism and colchicine unresponsiveness of FMF patients.

    PubMed

    Ozen, Filiz; Silan, Coskun; Uludag, Ahmet; Candan, Ferhan; Silan, Fatma; Ozdemir, Semra; Atik, Sinem; Ozdemir, Ozturk

    2011-01-01

    The multidrug resistance gene-1 (MDR1, adenosine triphosphate-binding cassette transporter: ABCB1, P-glycoprotein) encodes membrane proteins that play a crucial role in protecting cells from xenobiotics, chemicals, and drugs. The TT genotype of 3435 codon in exon 26 of MDR1 gene causes overexpression of gene activity and effluxes many chemically diverse compounds across the plasma membrane. We studied the association between C3435T polymorphisms (single nucleotide polymorphism) of MDR1 gene and colchicine-resistant familial Mediterranean fever (FMF) patients. Total genomic DNA samples from 52 FMF patients of colchicine unresponsiveness were used for FMF (MEFV) and MDR1 genes profile analyses. Target genes were genotyped by multiplex PCR-based reverse-hybridization Strip Assay method. The preliminary current results showed increased T allele frequency (0.596) in colchicine unresponsiveness of FMF patients. The distributions of the CC, CT, and TT genotypes in colchicine nonresponder FMF patients were 17%, 46%, and 37%, respectively. Our results indicate that C3435T polymorphism in exon 26 of MDR1 gene is associated with colchicine resistance in nonresponder FMF patients during the common therapy protocol.

  1. A phase Ib study of the effects of black raspberries on rectal polyps in patients with familial adenomatous polyposis.

    PubMed

    Wang, Li-Shu; Burke, Carol A; Hasson, Henrietta; Kuo, Chieh-Ti; Molmenti, Christine L Sardo; Seguin, Claire; Liu, Pengyuan; Huang, Tim H-M; Frankel, Wendy L; Stoner, Gary D

    2014-07-01

    Familial adenomatous polyposis (FAP) is characterized by the early onset of colonic polyposis and a high risk for colorectal cancer. FAP is treated by colectomy followed by lifelong removal of rectal polyps. This study determined whether black raspberries (BRBs) might regress rectal polyps in patients with FAP. Fourteen patients with FAP were treated with BRBs daily for 9 months. Seven patients received BRB powder orally plus two BRB suppositories inserted into the rectum at bedtime. The other 7 received an oral placebo plus the suppositories. Rectal polyp counts and polyp sizes were obtained at time zero and after 9 months of BRB treatment. Polyps and adjacent normal tissue were collected at both time points. The burden (P = 0.036) but not number (P = 0.069) of rectal polyps was significantly decreased. No benefit was noted with the addition of oral BRBs. Three patients were nonresponders. BRBs significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation, but not promoter methylation of the Wnt pathway antagonists, SFRP2 and WIF1, in rectal polyps (adenomas) from responders but not from nonresponders. The MBD-seq assay revealed more demethylated transcription start sites (TSS), including those for miRNAs, in BRB-treated adenomas from the responders. In conclusion, BRB suppositories seem sufficient for regressing rectal polyps in patients with FAP. ©2014 American Association for Cancer Research.

  2. Evaluation of the response to vaccination with hepatitis B vaccine in pediatric patients diagnosed with celiac disease

    PubMed Central

    Egberg, Matthew; Nelson, Catherine; Eickoff, Jens

    2014-01-01

    Background: A gap exists in the literature on celiac disease populations and the response to hepatitis B vaccination. Objective: To identify pediatric patients with celiac disease who received the primary hepatitis B vaccination and investigate their response to vaccine. Design/Methods: Patients underwent blood draw for hepatitis B surface antibody titers. Patients with undetectable or non-protective HBsAb titers were contacted. Study outcome measures and patient characteristics variables were summarized by means, standard deviations, medians, and ranges. A two-sample t-test was used to compare normally distributed continuous variables between responders and non-responders. Results: In all, 58% of patients did not meet the threshold for “protective” antibody titers. The mean time between completion of hepatitis B vaccination and diagnosis of celiac disease was 8.1 years for responders versus 10.5 years for non-responders. In a multivariate analysis, time between completion of vaccine and diagnosis of celiac disease was statistically significant predictor of response with an adjusted odds ratio of 0.69 (95% confidence interval: 0.50–0.95; p = 0.021). Conclusion: Our celiac disease population shows a high hepatitis B vaccine failure. The time between completion of vaccine series and diagnosis of celiac disease is an independent predictor for response. PMID:26770758

  3. Cardiovascular effects of indapamide in hypertensive patients with or without renal failure. A dose-response curve.

    PubMed

    Leenen, F H; Smith, D L; Farkas, R M; Boer, W H; Reeves, R A; Marquez-Julio, A

    1988-01-29

    Fifteen patients with mild-to-moderate hypertension (10 with normal and five with decreased renal function) were studied after treatment with placebo and low (1 mg), intermediate (2.5 mg), and high (5.0 mg per day) doses of indapamide, each for four weeks. Six patients--five with normal renal function--were classified as nonresponders (decrease in diastolic blood pressure less than 5 mm Hg). The remaining nine patients had dose-related decreases in blood pressure. Patients with or without renal failure showed similar decreases in blood pressure. Blood pressure reduction was associated with a significant decrease in cardiac index in the responders at the highest dose, related to a decrease in left ventricular end-diastolic dimension and stroke volume, whereas heart rate did not increase. This apparent decrease in venous return was associated with a significant decrease in body weight but not plasma volume in the responders. Indapamide did not change plasma norepinephrine levels, but decreased pressor responsiveness to exogenous norepinephrine. Responders had lower initial plasma renin activity and a smaller absolute increase in plasma renin activity while receiving indapamide, whereas angiotensin II pressor responsiveness was decreased more. The results presented indicate that the blood pressure lowering effect of indapamide in the present patient population is observed with or without renal failure and is associated with a decrease in pressor reactivity. In nonresponders, compensatory mechanisms (e.g., renin) may negate the antihypertensive effect of indapamide.

  4. Loss of Work Productivity and Quality of Life in Patients With Autoimmune Bullous Dermatoses.

    PubMed

    Heelan, K; Hitzig, S L; Knowles, S; Drucker, A M; Mittmann, N; Walsh, S; Shear, N H

    2015-01-01

    Little is known about quality of life and work productivity in autoimmune bullous dermatoses (AIBDs). To determine the impact of AIBDs on quality of life and work productivity. An observational cross-sectional study took place between February and May 2013 at an AIBD tertiary referral centre. Ninety-four patients were included. All participants completed the Dermatology Life Quality Index and the Work Productivity and Activity Impairment-Specific Health Problem questionnaires. Responders to treatment had less impairment (P<.001) than nonresponders. Patients with severe AIBD had significantly more impairment that those with mild (P<.001) and moderate (P=.002) AIBD. Greater impairment was associated with higher percentage of work missed. Those with a higher Dermatology Life Quality Index score had greater work impairment and overall activity impairment (P=.041, P=.024). Nonresponders had increased impairment while working (P<.001), overall work impairment (P<.001), and activity impairment (P<.001). Severely affected patients had worse impairment in all Work Productivity and Activity Impairment Questionnaire domains. AIBD has the potential to be a large burden on ability to work and quality of life. Larger studies are needed to clarify how these domains change over time and whether or not they improve with treatment. © The Author(s) 2015.

  5. Genetic polymorphisms, their allele combinations and IFN-β treatment response in Irish multiple sclerosis patients

    PubMed Central

    O’Doherty, Catherine; Favorov, Alexander; Heggarty, Shirley; Graham, Colin; Favorova, Olga; Ochs, Michael; Hawkins, Stanley; Hutchinson, Michael; O’Rourke, Killian; Vandenbroeck, Koen

    2009-01-01

    Introduction IFN-β is widely used as first-line immunomodulatory treatment for multiple sclerosis. Response to treatment is variable (30–50% of patients are nonresponders) and requires a long treatment duration for accurate assessment to be possible. Information about genetic variations that predict responsiveness would allow appropriate treatment selection early after diagnosis, improve patient care, with time saving consequences and more efficient use of resources. Materials & methods We analyzed 61 SNPs in 34 candidate genes as possible determinants of IFN-β response in Irish multiple sclerosis patients. Particular emphasis was placed on the exploration of combinations of allelic variants associated with response to therapy by means of a Markov chain Monte Carlo-based approach (APSampler). Results The most significant allelic combinations, which differed in frequency between responders and nonresponders, included JAK2–IL10RB–GBP1–PIAS1 (permutation p-value was pperm = 0.0008), followed by JAK2–IL10–CASP3 (pperm = 0.001). Discussion The genetic mechanism of response to IFN-β is complex and as yet poorly understood. Data mining algorithms may help in uncovering hidden allele combinations involved in drug response versus nonresponse. PMID:19604093

  6. Vaccination elicits correlated immune and clinical responses in glioblastoma multiforme patients.

    PubMed

    Wheeler, Christopher J; Black, Keith L; Liu, Gentao; Mazer, Mia; Zhang, Xiao-xue; Pepkowitz, Samuel; Goldfinger, Dennis; Ng, Hiushan; Irvin, Dwain; Yu, John S

    2008-07-15

    Cancer vaccine trials have failed to yield robust immune-correlated clinical improvements as observed in animal models, fueling controversy over the utility of human cancer vaccines. Therapeutic vaccination represents an intriguing additional therapy for glioblastoma multiforme (GBM; grade 4 glioma), which has a dismal prognosis and treatment response, but only early phase I vaccine trial results have been reported. Immune and clinical responses from a phase II GBM vaccine trial are reported here. IFN-gamma responsiveness was quantified in peripheral blood of 32 GBM patients given therapeutic dendritic cell vaccines. Posttreatment times to tumor progression (TTP) and survival (TTS) were compared in vaccine responders and nonresponders and were correlated with immune response magnitudes. GBM patients (53%) exhibited >or=1.5-fold vaccine-enhanced cytokine responses. Endogenous antitumor responses of similar magnitude occurred in 22% of GBM patients before vaccination. Vaccine responders exhibited significantly longer TTS and TTP relative to nonresponders. Immune enhancement in vaccine responders correlated logarithmically with TTS and TTP spanning postvaccine chemotherapy, but not with initial TTP spanning vaccination alone. This is the first report of a progressive correlation between cancer clinical outcome and T-cell responsiveness after therapeutic vaccination in humans and the first tracing of such correlation to therapeutically exploitable tumor alteration. As such, our findings offer unique opportunities to identify cellular and molecular components of clinically meaningful antitumor immunity in humans.

  7. Response to recombinant erythropoietin alpha, without the adjunct of granulocyte-colony stimulating factor, is associated with a longer survival in patients with transfusion-dependent myelodysplastic syndromes.

    PubMed

    Musto, Pellegrino; Villani, Oreste; Martorelli, Maria Carmen; Pietrantuono, Giuseppe; Guariglia, Roberto; Mansueto, Giovanna; D'Auria, Fiorella; Grieco, Vitina; Bianchino, Gabriella; Sparano, Anna; Zonno, Antonia; Lerose, Rosa; Sanpaolo, Grazia; Falcone, Antonietta

    2010-08-01

    This was a retrospective, comparative study focused on the extended follow-up of 192 transfusion-dependent patients with myelodysplastic syndromes treated (n. 83) or not treated (n. 109) with recombinant erythropoietin alpha (r-EPO) as single agent during the course of their disease. The results supported the safety of this treatment in the long term and also showed a significant survival advantage (median 52 months vs. 31 months, p<0.0095) in responding patients as compared to non-responding ones or to subjects never treated with r-EPO. At multivariate analysis, response to r-EPO maintained an independent prognostic value on OS.

  8. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials

    PubMed Central

    Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R

    2015-01-01

    Background: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Objectives: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Methods: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. Results: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. Conclusions: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. PMID:25583832

  9. Long-term safety and efficacy of dalfampridine for walking impairment in patients with multiple sclerosis: Results of open-label extensions of two Phase 3 clinical trials.

    PubMed

    Goodman, Andrew D; Bethoux, Francois; Brown, Theodore R; Schapiro, Randall T; Cohen, Ron; Marinucci, Lawrence N; Henney, Herbert R; Blight, Andrew R

    2015-09-01

    In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders. © The Author(s), 2015.

  10. Clinical and kidney morphologic predictors of outcome for renal artery stenting: data to inform patient selection.

    PubMed

    Modrall, J Gregory; Rosero, Eric B; Leonard, David; Timaran, Carlos H; Anthony, Thomas; Arko, Frank A; Valentine, R James; Clagett, G Patrick; Trimmer, Clayton

    2011-05-01

    The purpose of the current study was to identify clinical and kidney morphologic features that predict a favorable blood pressure (BP) response to renal artery stenting (RAS). The study cohort consisted of 149 patients who underwent primary RAS over 9 years. Patients were categorized as "responders" based on modified American Heart Association guidelines: BP <160/90 mm Hg on fewer antihypertensive medications or diastolic BP <90 mm Hg on the same medications. All other patients were deemed "nonresponders." Renal volume was estimated as kidney length × width × depth/2 based on preoperative computed tomography or magnetic resonance scans. Median follow-up was 19 months (interquartile range [IQR] 10.0-29.5 months). The median age of the cohort was 68 years (IQR, 60-74 years). A favorable BP response was observed in 50 of 149 patients (34%). Multivariate analysis identified three independent predictors of a positive BP response: (1) requirement for four or more medications (odds ratio, 29.9; P = .0001), (2) preoperative diastolic BP >90 mm Hg (OR, 31.4; P = .0011), and (3) preoperative clonidine use (OR, 7.3; P = .029). The BP response rate varied significantly based on the number of predictors present per patient (P < .0001). Among patients with three-drug hypertension, a larger ipsilateral kidney (volume ≥150 cm(3)) increased the BP response rate more than threefold compared with patients with smaller kidneys (63% vs 18% BP response rate; P = .018). The current study demonstrated that three clinical predictors (≥4 antihypertensive medications, diastolic BP ≥90 mm Hg, and clonidine use) are preoperative predictors of BP response to RAS. Kidney volume may help in discriminating responders from nonresponders among those patients with three-drug hypertension. These parameters may assist clinicians in patient selection and provide more concrete data with which to counsel patients on the likely outcomes for RAS. Published by Mosby, Inc.

  11. Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Payandeh, Mehrdad; Sohrabi, Nasrollah; Zare, Mohammad Erfan; Kansestani, Atefeh Nasir; Hashemian, Amir Hossein

    2012-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematological disorder characterized by auto antibody-mediated platelet destruction. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated. In recent years, many studies have demonstrated improvement of platelet counts in ITP patients after treating Helicobacter pylori infection. The aim of this study was to investigate the effects of H. pylori eradication on platelet count response in Iranian ITP patients. A total of 26 patients diagnosed with both ITP and H. pylori infection. ITP were diagnosed whose platelet counts were less than 100×103/μL. These patients were tested for H. pylori infection by Urea Breath Test and serum H. pylori antibody. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection. These patients followed for six months. Prevalence of H. pylori was 67.3%. H. pylori eradication achieved in 89.5% (26/29). Of the 26 patients, 15 (57.7%) exhibited a complete response (CR) and 11 (42.3%) were unresponsive. We did not find partial responders. There was a significant difference in the baseline platelet count of responders and non-responders patients (p<0.001). All responders had platelet count ≥50×103/μL and all non-responders had platelet count <50×103/μL. Results of this study revealed that eradication therapy of H. pylori infection can improve platelet counts in ITP patients especially with mild thrombocytopenia and support routine detection and treatment of H. pylori infection in ITP patients in populations with a high prevalence of this infection. PMID:22973500

  12. Portal hypertension in primary biliary cirrhosis (PBC): A reversible condition? Yes, but not in all UDCA treated patients.

    PubMed

    Huet, Pierre-Michel; Vincent, Catherine; Deslauriers, Julie; Coté, Jean; Fenyves, Daphna; Matsutani, Shoichi; Boileau, Robert; Kerckvoorde, Jacline Huet-Van

    2009-10-01

    Portal hypertension is not a rare complication of PBC, but there are no useful clinical predictors of its severity. In fact, in PBC patients, the evaluation of portal hypertension needs a direct access to the portal vein in order to measure the real porto-hepatic gradient (PHG), mainly because of a possible pre-sinusoidal component. The severity of portal hypertension, as measured by the PHG using a thin needle, correlated significantly with the long-term survival of PBC patients, but the initial Mayo score remained the best predictor of survival. In addition to the well-known effects on biological parameters, ursodeoxycholic acid (UDCA) treatment has been associated with a stabilization or improvement of portal hypertension but this effect was not observed in all patients: "responders" and "non-responders" to the UDCA could be identified according to changes in PHG and aspartate aminotransferase (AST) levels observed 2 years after UDCA therapy and had significantly different long-term survivals. This notion of "responders" and "non-responders" is new and may well explain the conflicting data found in the literature concerning the effects of UDCA in PBC patients as reported in various clinical trials. These findings are of interest when considering the emerging non-invasive methods aimed at evaluating liver fibrosis, particularly elastography that may prove useful in the indirect assessment of portal hypertension in the near future, therefore avoiding the need for the invasive measurement of the PHG.

  13. Elevated levels of T-cell immune response cDNA 7 in patients with immune thrombocytopenia.

    PubMed

    Zhu, Feng; Qiao, Jian-lin; Wu, Qing-yun; Cao, Jiang; Zeng, Ling-yu; Li, Zhen-yu; Xu, Kai-lin

    2014-12-01

    This study aimed to investigate the expression levels of T-cell immune response cDNA 7 (TIRC7) in immune thrombocytopenia (ITP) patients before and after high-dose dexamethasone (HD-DXM) treatment. Forty-four patients with ITP were enrolled and received dexamethasone (40 mg/day) for 4 consecutive days. Patients who had platelet counts more than 50 × 10(9)/l or less were defined as responders or non-responders, respectively. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to measure RNA level and plasma level of TIRC7, respectively. TIRC7 levels (RNA and plasma level) were significantly higher in ITP than that in control (P < 0.0001). However, after treatment, TIRC7 levels were significantly decreased in responders (P < 0.0001) but not in non-responders (P > 0.05). TIRC7 might be associated with the pathogenesis of ITP, and TIRC7 levels could be used as an indicator to evaluate patients' response to HD-DXM treatment.

  14. Phenotypic differences of CD4(+) T cells in response to red blood cell immunization in transfused sickle cell disease patients.

    PubMed

    Vingert, Benoît; Tamagne, Marie; Habibi, Anoosha; Pakdaman, Sadaf; Ripa, Julie; Elayeb, Rahma; Galacteros, Frédéric; Bierling, Philippe; Ansart-Pirenne, Hélène; Bartolucci, Pablo; Noizat-Pirenne, France

    2015-06-01

    Alloimmunization against red blood cells (RBCs) is the main immunological risk associated with transfusion in patients with sickle cell disease (SCD). However, about 50-70% of SCD patients never get immunized despite frequent transfusion. In murine models, CD4(+) T cells play a key role in RBC alloimmunization. We therefore explored and compared the CD4(+) T-cell phenotypes and functions between a group of SCD patients (n = 11) who never became immunized despite a high transfusion regimen and a group of SCD patients (n = 10) who had become immunized (at least against Kidd antigen b) after a low transfusion regimen. We studied markers of CD4(+) T-cell function, including TLR, that directly control lymphocyte function, and their spontaneous cytokine production. We also tested responders for the cytokine profile in response to Kidd antigen b peptides. Low TLR2/TLR3 expression and, unexpectedly, strong expression of CD40 on CD4(+) T cells were associated with the nonresponder status, whereas spontaneous expression of IL-10 by CD4(+) T cells and weak Tbet expression were associated with the responder status. A Th17 profile was predominant in responders when stimulated by Jb(k) . These findings implicate CD4(+) T cells in alloimmunization in humans and suggest that they may be exploited to differentiate responders from nonresponders. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Comparison of FDG-PET/CT and contrast-enhanced CT for monitoring therapy response in patients with metastatic breast cancer.

    PubMed

    Riedl, Christopher C; Pinker, Katja; Ulaner, Gary A; Ong, Leonard T; Baltzer, Pascal; Jochelson, Maxine S; McArthur, Heather L; Gönen, Mithat; Dickler, Maura; Weber, Wolfgang A

    2017-08-01

    The aim of this study was to compare fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and contrast-enhanced computed tomography (CE-CT) for the prediction of progression-free survival (PFS) and disease-specific survival (DSS) in patients with stage IV breast cancer undergoing systemic therapy. Sixty-five patients with metastatic breast cancer treated with first- or second-line systemic therapy in prospective clinical trials were included. Response to treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for CE-CT and by PET Response Criteria in Solid Tumors (PERCIST), respectively. All responders by RECIST (n = 22) were also responders by PERCIST, but 40% (17/43) of non-responders by RECIST were responders by PERCIST. Responses according to RECIST and PERCIST both correlated with PFS, but PERCIST showed a significantly higher predictive accuracy (concordance index for PFS: 0.70 vs. 0.60). One-year PFS for responders vs. non-responders by RECIST was 59% vs. 27%, compared to 63% vs. 0% by PERCIST. Four-year DSS of responders and non-responders by RECIST was 50% and 38%, respectively (p = 0.2, concordance index: 0.55) as compared to 58% vs. 18% for PERCIST (p < 0.001, concordance index: 0.65). Response on PET/CT was also a significantly better predictor for DSS than disease control on CE-CT. In patients with metastatic breast cancer, tumor response on PET/CT appears to be a superior predictor of PFS and DSS than response on CE-CT. Monitoring tumor response by PET/CT may increase the power of clinical trials using tumor response as an endpoint, and may improve patient management in clinical routine.

  16. Biological activity of interferon betas in patients with multiple sclerosis is affected by treatment regimen and neutralising antibodies

    PubMed Central

    Bertolotto, A; Sala, A; Malucchi, S; Marnetto, F; Caldano, M; Di, S; Capobianco, M; Gilli, F

    2004-01-01

    Background: MxA gene expression is one of the most appropriate markers of biological activity of exogenous interferon (IFN) beta. Methods: We quantified MxA mRNA for five consecutive days in 62 patients treated with IFN beta (16, Avonex; 10, Betaferon; 24, Rebif 22; 12, Rebif 44), by quantitative-competitive polymerase chain reaction. Every three months, IFN beta induced neutralising antibodies (NAbs) were evaluated in sera using a cytopathic effect assay. Results: Two categories of patients were identified: one group (49/62) had a sharp post-injection increase in MxA expression (defined as "IFN beta biological responder"), whereas the other group (13/62) had no MxA induction after IFN beta administrations (defined as "IFN beta biological non-responder"). In 11/13 biological non-responders, the persistent presence of NAbs correlated with abolished biological activity, independently of treatment regimen. The two remaining IFN beta biological non-responders were NAb–. Among the 49 IFN beta biological responders, biological activity was comparable between the four preparations on day 2 and 3 (+12 and +36 hours post-injection), but it was greater in Betaferon and both Rebif preparations on day 1, 4, and 5. In biological responders treated three times a week, only 82% (59/72) of injections were considered effective, compared with 100% (13/13) of Avonex injections. Conclusion: Our results suggest that an optimal IFN beta regimen is not yet available: Avonex, given once a week, shows lower cumulative biological activity. On the other hand, both Betaferon and Rebif, given three times a week, show 18% biologically ineffective injections and higher risk of developing NAbs, which abolish biological activity. PMID:15314118

  17. Clinical relevance of P-glycoprotein activity on peripheral blood mononuclear cells and polymorphonuclear neutrophils to methotrexate in systemic lupus erythematosus patients.

    PubMed

    García-Carrasco, Mario; Mendoza-Pinto, Claudia; Macías-Díaz, Salvador; Etchegaray-Morales, Ivet; Méndez-Martínez, Socorro; Soto-Santillán, Pamela; Pérez-Romano, Beatriz; Jiménez-Herrera, Erick A; Guzmán-Ruiz, Omar; Ruiz-Argüelles, Alejandro

    2017-06-14

    To elucidate the relationship between P-glycoprotein activity on peripheral blood leukocytes of systemic lupus erythematosus (SLE) patients with lupus arthritis and the clinical response to methotrexate. An observational study was made in patients with SLE according to ACR criteria 1997 who had arthralgia and arthritis and received methotrexate for ≥3 months. Methotrexate responders and non-responders were compared according to the Clinical Disease Activity Index. Mononuclear cells and polymorphonuclear neutrophils were isolated from SLE patients and P-glycoprotein expression was measured using the relative fluorescence index and percentage of positive cells. The chi-square test was used to compare P-glycoprotein activity between responders and non-responders. Thirty-two patients with a mean age of 45.4 ± 10.7 years were included: 34.4% had a response to methotrexate and 65.6% did not. Mean relative fluorescence units of both mononuclear cells and polymorphonuclear neutrophils were significantly lower in patients with a good response (7.0 ± 4.3 vs. 9.6 ± 3.8; p = 0.041 and 4.2 ± 3.5 vs. 7.6 ± 4.0; p = 0.004). The prevalence of low fluorescence levels (<6 relative fluorescence units), signifying higher P-glycoprotein activity of both mononuclear cells and polymorphonuclear neutrophils, was higher in methotrexate responders than in non-responders (27.3 vs. 4.8%; p = 0.10 and 81.8 vs. 23.8%; p = 0.003, respectively). In SLE patients with joint involvement treated with methotrexate, P-glycoprotein activity was higher in responders to methotrexate than in non-responders. Further studies are required to determine the mechanisms behind this finding and whether P-glycoprotein activity mediates alterations in methotrexate efficacy.

  18. A gene expression signature of CD34+ cells to predict major cytogenetic response in chronic-phase chronic myeloid leukemia patients treated with imatinib

    PubMed Central

    McWeeney, Shannon K.; Pemberton, Lucy C.; Loriaux, Marc M.; Vartanian, Kristina; Willis, Stephanie G.; Yochum, Gregory; Wilmot, Beth; Turpaz, Yaron; Pillai, Raji; Druker, Brian J.; Snead, Jennifer L.; MacPartlin, Mary; O'Brien, Stephen G.; Melo, Junia V.; Lange, Thoralf; Harrington, Christina A.

    2010-01-01

    In chronic-phase chronic myeloid leukemia (CML) patients, the lack of a major cytogenetic response (< 36% Ph+ metaphases) to imatinib within 12 months indicates failure and mandates a change of therapy. To identify biomarkers predictive of imatinib failure, we performed gene expression array profiling of CD34+ cells from 2 independent cohorts of imatinib-naive chronic-phase CML patients. The learning set consisted of retrospectively selected patients with a complete cytogenetic response or more than 65% Ph+ metaphases within 12 months of imatinib therapy. Based on analysis of variance P less than .1 and fold difference 1.5 or more, we identified 885 probe sets with differential expression between responders and nonresponders, from which we extracted a 75-probe set minimal signature (classifier) that separated the 2 groups. On application to a prospectively accrued validation set, the classifier correctly predicted 88% of responders and 83% of nonresponders. Bioinformatics analysis and comparison with published studies revealed overlap of classifier genes with CML progression signatures and implicated β-catenin in their regulation, suggesting that chronic-phase CML patients destined to fail imatinib have more advanced disease than evident by morphologic criteria. Our classifier may allow directing more aggressive therapy upfront to the patients most likely to benefit while sparing good-risk patients from unnecessary toxicity. PMID:19837975

  19. EEG-arousal regulation as predictor of treatment response in patients suffering from obsessive compulsive disorder.

    PubMed

    Dohrmann, Anna-Lena; Stengler, Katarina; Jahn, Ina; Olbrich, Sebastian

    2017-10-01

    Aim of this study was to analyze whether electroencephalogram (EEG)-based CNS-arousal markers differ for patients suffering from obsessive compulsive disorder (OCD) that either respond or do not respond to cognitive behavioral therapy (CBT), selective serotonin reuptake inhibitors (SSRIs) or their combination. Further the study aimed to identify specific response-predictors for the different therapy approaches. CNS-arousal from 51 unmedicated patients during fifteen-minute resting state was assessed using VIGALL (Vigilance Algorithm Leipzig). Clinical Global Impression (CGI) scores were used to assess response or non-response after three to six months following therapy (CBT, n=18; SSRI, n=11 or combination, n=22). Differences between Responders (R) and Non-Responders (NR) were identified using multivariate analysis of covariance (MANCOVA) models. MANCOVA revealed that Responders spent significant less time at the highest CNS-arousal stage 0. Further, low amounts of the highest CNS-arousal stages were specifically predictive for a response to a combined treatment approach. The fact that CNS-arousal markers allowed discrimination between Responders and Non-Responders and also between Responders of different treatment arms underlines a possible clinical value of EEG-based markers. These results encourage further research on EEG-arousal regulation for determining pathophysiological subgroups for treatment response. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  20. Cholinesterase inhibitors are compatible with psychosocial intervention for Alzheimer disease patients suggested by neuroimaging findings.

    PubMed

    Meguro, Kenichi

    2017-01-30

    We previously reported that the frontal lobe was stimulated by psychosocial intervention for dementia patients, and that the parietal lobe was associated with logical judgment. We hypothesized that the combined therapeutic approach with symptomatic drug treatment can directly stimulate not only attention function but also judgment function indirectly to observing other participants' behaviors. Fifty-two patients with Alzheimer disease underwent the group reminiscence approach with reality orientation, as well as the donepezil treatment. The cerebral blood flow (CBF) was assessed with (99m)Tc-ECD SPECT. Two analyses were performed: Analysis 1 was to compare Responders vs. Non-responders as shown by MMSE scores, whereas Analysis 2 was to compare Good vs. Poor reminders of the intervention content. We found that the CBF in the frontal lobe was significantly higher in Responders (vs. Non-responders). The CBF in the parietal lobe, especially the left side, was significantly higher in the Good reminders (vs. Poor reminders). The donepezil stimulated the areas similar to where the psychosocial intervention was previously found to be stimulated directly, thus the drug was thought to be compatible for psychosocial intervention. The parietal lobe was stimulated indirectly, suggesting that the indirect effect of the intervention may be based on logical judgment function.

  1. Relationship between response to colchicine treatment and MDR1 polymorphism in familial Mediterranean fever patients.

    PubMed

    Uludag, Ahmet; Silan, Coskun; Atik, Sinem; Akurut, Cisem; Uludag, Aysegul; Silan, Fatma; Ozdemir, Ozturk

    2014-02-01

    Investigate the relationship between MDR1 C3435T polymorphism and colchicine response in Familial Mediterranean fever (FMF) patients. Patients (n=50) who received colchicine regularly, were willing to participate in the study, and attended control visits were included in the study. MDR1 C3435T genotype was defined by the real-time polymerase chain reaction method. Patients were divided into three groups. Patients, who recovered from episodes with standard colchicine treatment, and had no attack in the last 1 year were accepted as complete; patients whose episode number and intensity were decreased with the ongoing standard treatment as partial; and patients whose episodes were not decreased despite the standard treatment as nonresponders. MDR1 C and T allele frequencies of FMF patients with colchicine responses of complete, partial, and nonresponders were C=0.75 and T=0.25; C=0.56 and T=0.44; and C=0.50 and T=0.50, respectively. When complete responding patients were compared with the partial responding patients, subjects with CT genotype had 6.18 times more increased risk than with CC genotype (OR=6.18; p=0.015). Poor response risk of subjects with the T allele was increased 2.45 times more when compared with the C allele (p=0.03). MDR1 gene C3435T polymorphism enacts an important role on colchicine response in FMF; good response to colchicine treatment was related to the C allele, whereas poor response was related to the T allele in FMF.

  2. Per cent of patients with chronic migraine who responded per onabotulinumtoxinA treatment cycle: PREEMPT

    PubMed Central

    Silberstein, Stephen D; Dodick, David W; Aurora, Sheena K; Diener, Hans-Christoph; DeGryse, Ronald E; Lipton, Richard B; Turkel, Catherine C

    2015-01-01

    Objective The approved use of onabotulinumtoxinA for prophylaxis of headaches in patients with chronic migraine (CM) involves treatment every 12 weeks. It is currently unknown whether patients who fail to respond to the first onabotulinumtoxinA treatment cycle will respond to subsequent treatment cycles. To help inform decisions about treating non-responders, we examined the probability of treatment cycle 1 non-responders responding in cycle 2, and cycle 1 and 2 non-responders responding in cycle 3. Methods Pooled PREEMPT data (two studies: a 24-week, 2-cycle, double-blind, randomised (1:1), p