Treatment Outcomes of Treatment-Naïve Hepatitis C Patients co-infected with HIV: a systematic review and meta-analysis of observational cohorts

Co-infection with Hepatitis C (HCV) and HIV is common and HIV accelerates hepatic disease progression due to HCV. However, access to HCV treatment is limited and success rates are generally poor

Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership (Grant IP.2007.32011.011), US Agency for International Development, UK Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, National Institutes of Health, AIDS Clinical Trials Group. The study was also supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426). Bayer Healthcare for donated moxifloxacin and Sanofi donated rifampin.Background:  The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. Methods:  Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses. Results:  Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24–41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318–535). Pre-treatment spot samples had a higher yield of positive Ziehl–Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan–Meier analyses in either EMS or spot samples. Conclusions:  Our data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples.Publisher PDFPeer reviewe

Pretreatment chest x-ray severity and its relation to bacterial burden in smear positive pulmonary tuberculosis

Background Chest radiographs are used for diagnosis and severity assessment in tuberculosis (TB). The extent of disease as determined by smear grade and cavitation as a binary measure can predict 2-month smear results, but little has been done to determine whether radiological severity reflects the bacterial burden at diagnosis. Methods Pre-treatment chest x-rays from 1837 participants with smear-positive pulmonary TB enrolled into the REMoxTB trial (Gillespie et al., N Engl J Med 371:1577–87, 2014) were retrospectively reviewed. Two clinicians blinded to clinical details using the Ralph scoring system performed separate readings. An independent reader reviewed discrepant results for quality assessment and cavity presence. Cavitation presence was plotted against time to positivity (TTP) of sputum liquid cultures (MGIT 960). The Wilcoxon rank sum test was performed to calculate the difference in average TTP for these groups. The average lung field affected was compared to log 10 TTP by linear regression. Baseline markers of disease severity and patient characteristics were added in univariable regression analysis against radiological severity and a multivariable regression model was created to explore their relationship. Results For 1354 participants, the median TTP was 117 h (4.88 days), being 26 h longer (95% CI 16–30, p < 0.001) in patients without cavitation compared to those with cavitation. The median percentage of lung-field affected was 18.1% (IQR 11.3–28.8%). For every 10-fold increase in TTP, the area of lung field affected decreased by 11.4%. Multivariable models showed that serum albumin decreased significantly as the percentage of lung field area increased in both those with and without cavitation. In addition, BMI and logged TTP had a small but significant effect in those with cavitation and the number of severe TB symptoms in the non-cavitation group also had a small effect, whilst other factors found to be significant on univariable analysis lost this effect in the model. Conclusions The radiological severity of disease on chest x-ray prior to treatment in smear positive pulmonary TB patients is weakly associated with the bacterial burden. When compared against other variables at diagnosis, this effect is lost in those without cavitation. Radiological severity does reflect the overall disease severity in smear positive pulmonary TB, but we suggest that clinicians should be cautious in over-interpreting the significance of radiological disease extent at diagnosis

Measurement of J/Psi and Psi(2S) Polarization in ppbar Collisions at sqrt(s) = 1.8 TeV

We have measured the polarization of J/Psi and Psi(2S) mesons produced in p\bar{p} collisions at \sqrt{s} = 1.8 TeV, using data collected at CDF during 1992-95. The polarization of promptly produced J/Psi [Psi(2S)] mesons is isolated from those produced in B-hadron decay, and measured over the kinematic range 4[5.5] < P_T < 20 GeV/c and |y| < 0.6. For P_T \gessim 12 GeV/c we do not observe significant polarization in the prompt component.Comment: Revised version, accepted for publication in Physical Review Letter

Toxicity related to standard TB therapy for pulmonary tuberculosis and treatment outcomes in the REMoxTB study according to HIV status

Abstract Background The phase III REMoxTB study prospectively enrolled HIV-positive (with CD4+ count > 250 cells, not on anti-retroviral therapy) and HIV-negative patients. We investigated the incidence of adverse events and cure rates according to HIV status for patients receiving standard TB therapy in the trial. Methods Forty-two HIV-positive cases were matched to 220 HIV-negative controls by age, gender, ethnicity, and trial site using coarsened exact matching. Grade 3 and 4 adverse events (AEs) were summarised by MedDRA System Organ Class. Kaplan-Meier curves for time to first grade 3 or 4 AE were constructed according to HIV status with hazard ratios calculated. Patients were considered cured if they were culture negative 18 months after commencing therapy with ≥2 consecutive negative culture results. Results Twenty of 42 (47.6%) HIV-positive and 34 of 220 (15.5%) HIV-negative patients experienced ≥1 grade 3 or 4 AE, respectively. The majority of these were hepatobiliary disorders that accounted for 12 of 40 (30.0%) events occurring in 6 of 42 (14.3%) HIV-positive patients and for 15 of 60 (25.0%) events occurring in 9 of 220 (4.1%) HIV-negative patients. The median time to first grade 3 or 4 AE was 54 days (IQR 15.5–59.0) for HIV-positive and 29.5 days (IQR 9.0–119.0) for HIV-negative patients, respectively. The hazard ratio for experiencing a grade 3 or 4 AE among HIV-positive patients was 3.25 (95% CI 1.87–5.66, p < 0.01). Cure rates were similar, with 38 of 42 (90.5%) HIV-positive and 195 of 220 (88.6%) HIV-negative patients (p = 0.73) cured at 18 months. Conclusions HIV-positive patients receiving standard TB therapy in the REMoxTB study were at greater risk of adverse events during treatment but cure rates were similar when compared to a matched sample of HIV-negative patients

Measurement of the Strong Coupling Constant from Inclusive Jet Production at the Tevatron pˉp\bar pp Collider

We report a measurement of the strong coupling constant, $\alpha_s(M_Z)$, extracted from inclusive jet production in $p\bar{p}$ collisions at $\sqrt{s}=$1800 GeV. The QCD prediction for the evolution of $\alpha_s$ with jet transverse energy $E_T$ is tested over the range 40<$E_T$<450 GeV using $E_T$ for the renormalization scale. The data show good agreement with QCD in the region below 250 GeV. In the text we discuss the data-theory comparison in the region from 250 to 450 GeV. The value of $\alpha_s$ at the mass of the $Z^0$ boson averaged over the range 40<$E_T$<250 GeV is found to be $\alpha_s(M_{Z})= 0.1178 \pm 0.0001{(\rm stat)}^{+0.0081}_{-0.0095}{\rm (exp. syst)}$. The associated theoretical uncertainties are mainly due to the choice of renormalization scale (^{+6%}_{-4%}) and input parton distribution functions (5%).Comment: 7 pages, 3 figures, using RevTeX. Submitted to Physical Review Letter

Observation of Hadronic W Decays in t-tbar Events with the Collider Detector at Fermilab

We observe hadronic W decays in t-tbar -> W (-> l nu) + >= 4 jet events using a 109 pb-1 data sample of p-pbar collisions at sqrt{s} = 1.8 TeV collected with the Collider Detector at Fermilab (CDF). A peak in the dijet invariant mass distribution is obtained that is consistent with W decay and inconsistent with the background prediction by 3.3 standard deviations. From this peak we measure the W mass to be 77.2 +- 4.6 (stat+syst) GeV/c^2. This result demonstrates the presence of two W bosons in t-tbar candidates in the W (-> l nu) + >= 4 jet channel.Comment: 20 pages, 4 figures, submitted to PR

Search for the Supersymmetric Partner of the Top-Quark in ppˉp \bar{p} Collisions at s=1.8TeV\sqrt{s} = 1.8 {\rm TeV}

We report on a search for the supersymmetric partner of the top quark (stop) produced in $t \bar{t}$ events using $110 {\rm pb}^{-1}$ of $p \bar{p}$ collisions at $\sqrt{s} = 1.8 {\rm TeV}$ recorded with the Collider Detector at Fermilab. In the case of a light stop squark, the decay of the top quark into stop plus the lightest supersymmetric particle (LSP) could have a significant branching ratio. The observed events are consistent with Standard Model $t \bar{t}$ production and decay. Hence, we set limits on the branching ratio of the top quark decaying into stop plus LSP, excluding branching ratios above 45% for a LSP mass up to 40 {\rm GeV/c}$^{2}$.Comment: 11 pages, 4 figure

Search for Narrow Diphoton Resonances and for gamma-gamma+W/Z Signatures in p\bar p Collisions at sqrt(s)=1.8 TeV

We present results of searches for diphoton resonances produced both inclusively and also in association with a vector boson (W or Z) using 100 pb^{-1} of p\bar p collisions using the CDF detector. We set upper limits on the product of cross section times branching ratio for both p\bar p\to\gamma\gamma + X and p\bar p\to\gamma\gamma + W/Z. Comparing the inclusive production to the expectations from heavy sgoldstinos we derive limits on the supersymmetry-breaking scale sqrt{F} in the TeV range, depending on the sgoldstino mass and the choice of other parameters. Also, using a NLO prediction for the associated production of a Higgs boson with a W or Z boson, we set an upper limit on the branching ratio for H\to\gamma\gamma. Finally, we set a lower limit on the mass of a `bosophilic' Higgs boson (e.g. one which couples only to \gamma, W, and Z$ bosons with standard model couplings) of 82 GeV/c^2 at 95% confidence level.Comment: 30 pages, 11 figure

Production of Y(1S) Mesons from chib Decays in pp(bar) Collisions at sqrt(s)=1.8 TeV

We have reconstructed the radiative decays $\chi_{b}(1P) \to \Upsilon(1S) \gamma$ and $\chi_{b}(2P) \to \Upsilon(1S) \gamma$ in $p \bar{p}$ collisions at $\sqrt{s} = 1.8$ TeV, and measured the fraction of $\Upsilon(1S)$ mesons that originate from these decays. For $\Upsilon(1S)$ mesons with $p^{\Upsilon}_{T}>8.0$ GeV/$c$, the fractions that come from $\chi_{b}(1P)$ and $\chi_{b}(2P)$ decays are $(27.1\pm6.9(stat)\pm4.4(sys))$ and $(10.5\pm4.4(stat)\pm1.4(sys))$, respectively. We have derived the fraction of directly produced $\Upsilon(1S)$ mesons to be $(50.9\pm8.2(stat)\pm9.0(sys))$.Comment: 13 Pages, 2 figure