Contemporary HCV pangenotypic DAA treatment protocols are exclusionary to real world HIV-HCV co-infected patients.

BACKGROUND: Treatments for Hepatitis C virus (HCV) infection have vastly improved over the past few decades with current regimens now offering pangenotypic activity with excellent cure rates reported in clinical trials, including in the HIV-HCV coinfected population. However, there is some concern that stringent inclusion and exclusion criteria in the trials may lead to results that are not achievable in real-world populations. METHODS: Our study evaluated a real-world HIV-HCV coinfected population and compared them to the eligibility criteria for trials of two of the most recent approved HCV agents; sofosbuvir/velpatasvir and glecaprevir/pibrentasvir. RESULTS: Our study included 219 HIV-HCV coinfected patients and found that 89% met exclusion criteria for the sofosbuvir/velpatasvir trial and 90% met exclusion criteria for the glecaprevir/pibrentasvir trial. The majority of patients met more than one exclusion criteria with the most frequent criteria for exclusion being a non-approved ART regimen (58 and 47% respectively), having a psychiatric disorder (52%), active alcohol or injection drug use (27%), having an HIV viral load > 50 copies/ml (15%), a CrCl < 60 ml/min (13%) and a history of decompensated cirrhosis (13%). CONCLUSION: Although the newer Hepatitis C treatments are very effective, the real world HIV-HCV coinfected population often have comorbidities and other characteristics that make them ineligible for clinical trials, such that they are barriers to treatment. These barriers need to be recognized and addressed in order to optimize treatment outcomes in the HIV patient population.

Management of treatment-naïve chronic hepatitis C genotype 1 patients: a cost-effectiveness analysis of treatment options.

New and more promising therapies for chronic hepatitis C (CHC) genotype 1 (G1) naive patients have recently been approved in the United States and Europe, and several more regimens are expected to become available within the next several years. While this scenario unfolds, it is necessary to develop a rational method to allocate current treatment in CHC G1 patients. We performed a cost-effectiveness analysis of boceprevir (BOC)- and telaprevir (TVR)-based triple therapy according to different patients' selection strategies. A semi-Markov model of CHC natural history and progression towards end-stage liver disease was built. We considered 3 selection strategies based on METAVIR fibrosis stage: (i) treat all patients with F1-F4 fibrosis, (ii) only F2-F4 and (iii) only F3-F4. For each strategy, TVR interleukin-28B-guided (IL28B-guided) and BOC rapid virologic response-guided (RVR-guided) therapies were applied. The model assessed the costs and outcomes, using a lifetime and 5-year time horizon, and adopting the Italian National Health System perspective. The incremental cost-effectiveness ratio (ICER) for F1-F4 strategy relative to F3-F4 was €5132 per quality-adjusted life years gained, across TVR IL-28B-guided therapy, and €7042 in the BOC RVR-guided therapy. Conversely, in the 5-year scenario, the ICER for F1-F4 strategy relative to F3-F4 was €1 818 679 (TVR IL28B-guided) and €1 866 437 (BOC RVR-guided) per end-stage liver disease or death (ESLD-D) avoided. In view of anticipated improvement in the efficacy of future regimens, selective treatment of only patients with advanced fibrosis and cirrhosis with TVR or BOC could represent the most cost-effective strategy to optimize resource utilization.

Radiologic and laboratory differences in patients with tuberculous and parapneumonic pleural effusions showing non-lymphocytic predominance and high adenosine deaminase levels.

PURPOSE: Tuberculous pleural effusion (TPE) is characterized by lymphocytic predominance and high adenosine deaminase (ADA) levels. However, TPEs sometimes present non-lymphocytic predominance, and parapneumonic effusion (PPE) often exceeds the cutoff value of ADA for TPE. Thus, the differential diagnosis of cases with pleural fluid (PF) showing non-lymphocytic predominance and high ADA levels is challenging. However, limited data concerning the clinical differences in these patients are available. METHODS: A retrospective study was conducted on TPE and PPE patients with PF showing non-lymphocytic predominance and ADA levels ≥40 U/L in 2009-2013 in a South Korean tertiary referral hospital. The clinical, laboratory, and computed tomography (CT) findings between the groups were analyzed using multivariate logistic regression to develop a prediction model with independent factors for TPE. RESULTS: Among 353 patients with TPE, 24 (6.8 %) showed PF with non-lymphocytic predominance and ADA levels of ≥40 U/L. Twenty-eight PPE patients who presented PF findings comparable with those of TPE patients were included in the control group. In the final analysis, PF ADA levels >58 U/L and nodular lung lesions on CT were independent positive predictors, while loculated effusion was an independent negative predictor for TPE. Using the prediction model, a score ≥ +3 provided a sensitivity of 88 %, specificity of 93 %, positive predictive value of 91 %, and negative predictive value of 90 % for TPE. CONCLUSION: PF ADA levels, nodular lung lesions, and loculated pleural effusion may help differentiate TPE from PPE in patients with PF showing non-lymphocytic predominance and ADA levels ≥40 U/L.

Kinetic studies and thermodynamics of oil extraction and transesterification of Chlorella sp. for biodiesel production.

In this work, a mixture of chloroform and methanol (1:1, v/v) was applied to oil extraction from Chlorella sp. at 30, 40, 50 and 60 degrees C for 150 min extraction times. Kinetic studies revealed that the values of n and the rate constants were found to depend strongly on temperature. The activation energy was Ea = 38.893 kJ/mol, and the activation thermodynamic parameters at 60 degrees C were ΔS≠ = -180.190 J/mol , ΔH≠ = 36.124k J/mol and ΔG≠ = 96.128k J/mol. Both ΔH and ΔS yielded positive values, whereas ΔG was negative at 60 degrees C, indicating that this process is endothermic, irreversible and spontaneous. The acidic transesterification process was also investigated by gas chromatographic analysis of the microalgae fatty acid methyl esters (biodiesel) at different temperatures and reaction times. The fatty acid profile indicated that the main components were palmitic, linoleic and linolenic acids. The concentration of linolenic acid increased and oleic acid decreased as the temperature increased. Two-hour transesterification is the best reaction time for biodiesel production because it produces the highest percentage of unsaturated fatty acids (74%). These results indicate the potential of Chlorella sp. to produce biodiesel of good quality.

Comparison of harvesting methods for microalgae Chlorella sp. and its potential use as a biodiesel feedstock.

Three methods for harvesting Chlorella sp. biomass were analysed in this paper--centrifugation, membrane microfiltration and coagulation: there was no significant difference between the total amount of biomass obtained by centrifugation and membrane microfiltration, i.e., 0.1174 +/- 0.0308 and 0.1145 +/- 0.0268 g, respectively. Almost the same total lipid content was obtained using both methods, i.e., 27.96 +/- 0.77 and 26.43 +/- 0.67% for centrifugation and microfiltration, respectively. However, harvesting by coagulation resulted in the lowest biomass and lipid content. Similar fatty acid profiles were obtained for all of the harvesting methods, indicating that the main components were palmitic acid (C16:0), oleic acid (C18:1) and linoleic acid (C18:2). However, the amounts of the individual fatty acids were higher for microfiltration than for centrifugation and coagulation; coagulation performed the most poorly in this regard by producing the smallest amount of fatty acids (41.61 +/- 6.49 mg/g dw). The harvesting method should also be selected based on the cost benefit and energy requirements. The membrane filtration method offers the advantages of currently decreasing capital costs, a high efficiency and low maintenance and energy requirements and is thus the most efficient method for microalgae harvesting.

Predictive factors for tuberculosis in patients with a TB-PCR-negative bronchial aspirate.

PURPOSE: Pulmonary tuberculosis (PTB), with a tuberculosis (TB)-polymerase chain reaction (PCR)-negative bronchial aspirate (BA), but a positive culture result is often encountered in clinical practice. However, limited data are available concerning clinical judgment in patients with suspected PTB and a TB-PCR-negative BA pending culture results. The present study aimed to identify predictors for PTB in patients with a TB-PCR-negative BA. METHODS: A retrospective study was conducted on patients who had undergone a bronchoscopy because of suspected PTB. Clinical, laboratory, and computed tomography (CT) findings were investigated in PTB patients with TB-PCR-negative but positive culture BA results, and non-PTB patients with a radiographic lesion comparable to the former. RESULTS: Of 250 patients screened, 31 (12 %) were diagnosed with PTB by positive culture results only. Of these 31 patients, 30 (97 %) had a lesion within one-third of the hemithorax as determined by chest radiography. In the final analysis of 30 PTB and 65 non-PTB patients with comparable radiographic lesions, a positive QuantiFERON-TB Gold In-Tube (QFT) result was independently associated with an increased risk of a positive TB culture. CT findings of consolidation were a negative predictor for PTB. Patients with a negative QFT result and consolidation had a negative predictive value of 95 % for PTB, while patients with a positive QFT result and nodular CT abnormalities without consolidation had a positive predictive value of 86 % for PTB. CONCLUSION: The simple combination of CT findings of consolidation and QFT test results may help clinicians to refine decision-making in patients with a TB-PCR-negative BA.

Providing essential clinical care for non-COVID-19 patients in a Seoul metropolitan acute care hospital amidst ongoing treatment of COVID-19 patients.

We assessed infection control efforts by comparing data collected over 20 weeks during a pandemic under a dual-track healthcare system. A decline in non-COVID-19 patients visiting the emergency department by 37.6% (P<0.01) was observed since admitting COVID-19 cases. However, patients with acute myocardial infarction (AMI), stroke, severe trauma and acute appendicitis presenting for emergency care did not decrease. Door-to-balloon time (34.3 (± 11.3) min vs 22.7 (± 8.3) min) for AMI improved significantly (P<0.01) while door-to-needle time (55.7 (± 23.9) min vs 54.0 (± 18.0) min) in stroke management remained steady (P=0.80). Simultaneously, time-sensitive care involving other clinical services, including patients requiring chemotherapy, radiation therapy and haemodialysis did not change.

Catalytic co-pyrolysis of sugarcane bagasse and waste high-density polyethylene over faujasite-type zeolite.

This study investigated the catalytic co-pyrolysis of sugarcane bagasse (SCB) and waste high-density polyethylene (HDPE) over faujasite-type zeolite derived from electric arc furnace slag (FAU-EAFS) in a fixed-bed reactor. The effects of reaction temperature, catalyst-to-feedstock ratio, and HDPE-to-SCB ratio on product fractional yields and chemical compositions were discussed. The co-pyrolysis of SCB and HDPE over FAU-EAFS increased the liquid yield and enhanced the quality of bio-oil. The maximum bio-oil (68.56 wt%) and hydrocarbon yield (74.55%) with minimum yield of oxygenated compounds (acid = 0.57% and ester = 0.67%) were achieved under the optimum experimental conditions of catalyst-to-feedstock ratio of 1:6, HDPE-to-SCB ratio of 40:60, and temperature of 500 °C. The oil produced by catalytic co-pyrolysis had higher calorific value than the oil produced by the pyrolysis of SCB alone.

An expert consensus for the management of chronic hepatitis B in Asian Americans.

BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM: To generate recommendations for the management of Asian Americans infected with HBV. METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS: Asian American patients, HBeAg positive or negative, with HBV DNA levels >2000 IU/mL (>104 copies/mL) and ALT values above normal are candidates for anti-viral therapy. HBeAg negative patients with HBV DNA >2000 IU/mL and normal ALT levels but who have either serum albumin <3.5 g/dL or platelet count <130 000 mm3 , basal core promoter (BCP) mutations, or who have first-degree relatives with HCC should be offered treatment. Patients with cirrhosis and detectable HBV DNA must receive life-long anti-viral therapy. Indications for treatment include pregnant women with high viraemia, coinfected patients, and those requiring immunosuppressive therapy. In HBsAg positive patients with risk factors, life-long surveillance for HCC with alpha-fetoprotein (AFP) testing and abdominal ultrasound examination at 6-month intervals is required. In CHB patients receiving HCC treatments, repeat imaging with contrast CT scan or MRI at 3-month intervals is strongly recommended. These guidelines have been assigned to a Class (reflecting benefit vs. risk) and a Level (assessing strength or certainty) of evidence. CONCLUSIONS: Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes.

Psychometric properties of the PROMIS short form measures in a U.S. cohort of 961 patients with chronic hepatitis C prescribed direct acting antiviral therapy.

BACKGROUND: To better understand symptoms experienced by patients infected with chronic hepatitis C virus (HCV), valid and reliable patient-reported outcome (PRO) measures are needed. AIM: To assess the reliability and validity of 10 patient-reported outcomes measurement information system (PROMIS) measures and the Headache Impact Test-6 (HIT-6) in a large national sample of patients with HCV. METHODS: Pre-treatment data from 961 patients with HCV starting direct acting antiviral therapy at 11 U.S. liver centers were analyzed. Internal reliability was evaluated using Cronbach's alpha coefficient; frequency distributions were examined for floor and ceiling effects; structural validity was investigated via item-response-theory models; convergent validity was evaluated using correlations with theoretically-similar items from the HCV-PRO and memorial symptom assessment scale (MSAS); and known-groups validity was investigated by observing PRO differences by liver disease status and number of comorbidities. RESULTS: The HIT-6 and the majority of the PROMIS measures yielded excellent reliability (alphas ≥ 0.87). Ceiling effects were infrequent ( < 4%), while 30%-59% of patients reported no symptoms (floor effects). The data supported structural validity of the HIT-6 and most PROMIS measures. The PROMIS measures showed moderate to strong correlations with theoretically-similar items from the HCV-PRO and MSAS (0.39-0.77). Trends were observed between worse PRO scores and advanced cirrhosis and greater number of comorbidities, lending support for known-groups validity. CONCLUSIONS: The psychometric properties of the HIT-6 and PROMIS measures performed satisfactorily in this large cohort of patients with HCV starting direct acting antiviral therapy. Opportunities exist for further refinement of these PROs. Evaluation of performance over time and in under-represented subgroups is needed.

Biophoton emission of MDCK cell with hydrogen peroxide and 60 Hz AC magnetic field.

We studied biophoton characteristics of Madin-Darby canine kidney (MDCK) cells under the influence of H2O2 by employing a photomultiplier tube (PMT) and a fluorescence microscope. H2O2 was used for producing reactive oxygen species (ROS) in the measurement. Images from a fluorescence microscope show an increase of photon intensity emitted from the sample due to H2O2. By using a PMT we measured quantitative change in biophoton emission with application of H2O2 to the MDCK cell culture, found that the increase of the biophoton is dependent upon the amount of H2O2. The agreement between the results of the PMT and the fluorescence microscope suggests the possibility of quantitative measurement of the influence of ROS on living tissue or cell. In addition we applied a 60 HzAC magnetic field on the cells to investigate the change in reaction between MDCK cell and ROS. It showed that a decay of chemiluminescence intensity has taken a different path following exposure to the magnetic field. As a result, the PMT measurement might be considered as a useful tool for studying biochemical characteristics in relation to ROS.

Survival after treatment with curative intent for hepatocellular carcinoma among patients with vs without non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is expected to become a leading aetiology of hepatocellular carcinoma (HCC)-related mortality in the United States. HCC treatments with curative intent (OLT, orthotopic liver transplantation; resection; RFA, radiofrequency ablation) can improve survival in carefully selected patients. AIM: To compare survival after receipt of curative treatment for NAFLD and non-NAFLD-HCC aetiologies (HCV, chronic hepatitis C; HBV, chronic hepatitis B; ALD, alcoholic liver disease) and by treatment was performed. METHODS: A cohort of 17 664 patients was assembled using linked Surveillance, Epidemiology, and End Results and Medicare data from 1991 to 2011 with confirmed diagnosis of HCC. RESULTS: The cohort was mostly male, aged 70 (21-106) years, without cardiovascular disease, and had liver cirrhosis without decompensation, metastatic HCC or large tumour size (>5 cm). The NAFLD-HCC group was mostly female and older with more cardiovascular disease, metastatic HCC, and large tumour size and less cirrhosis and decompensated liver disease than the non-NAFLD-HCC groups. The NAFLD group was 47% less likely to receive any curative treatment as compared with non-NAFLD aetiologies (OR 0.53, P < .001). NAFLD-HCC had worse median survival after OLT (3.2, 0-12.9 years, P = .01) but had improved survival after resection (2.4, 0-12.0 years, P < .001) as compared with non-NAFLD-HCC. No significant survival differences existed for RFA by HCC aetiology. NAFLD was not an independent predictor of mortality after OLT, resection or RFA. CONCLUSION: Patients with NAFLD-HCC had worse survival after OLT but favourable survival after resection, particularly in the absence of cirrhosis, as compared with non-NAFLD-HCC aetiologies.

All-oral direct-acting antiviral therapy in HCV-advanced liver disease is effective in real-world practice: observations through HCV-TARGET database.

BACKGROUND: Chronic hepatitis C virus therapy in patients with advanced liver disease remains a clinical challenge. HCV-TARGET collects data in patients treated at tertiary academic and community centres. AIM: To assess efficacy of all-oral HCV therapy in advanced liver disease. METHODS: Between December 2013 and October 2014, 240 patients with a MELD score of ≥10 initiated HCV treatment with an all-oral regimen. Data from the 220 patients who completed 12-week follow-up were analysed. RESULTS: Genotype 1 (GT1) patients had higher sustained virological response (SVR) when treated with sofosbuvir plus simeprevir ± ribavirin than with sofosbuvir plus ribavirin (66-74% vs. 54%); GT1b vs GT1a (84% vs. 64%). SVR for GT2 was 72% with sofosbuvir plus ribavirin, while GT3 patients had a substantially lower response (35%). A decrease in MELD score was not clearly related to SVR over the short course of follow-up although some had improvements in MELD score, serum bilirubin and albumin. A predictor of virological response was albumin level while negative predictors were elevated bilirubin level and GT1a. Most patients with GT1 were treated with approximately 12-week duration of sofosbuvir and simeprevir ± ribavirin therapy while GT2 and GT3 patients were treated with approximately 12 and 24 weeks of sofosbuvir plus ribavirin respectively. CONCLUSIONS: All-oral therapies are effective among patients with advanced liver disease with high levels of success in GT2 and GT1b, and may serve to reduce the severity of liver disease after SVR. Treatment for GT3 patients remains an unmet need. Clinical trial number: NCT01474811.

Cloning, expression, and characterization of a methionyl aminopeptidase from a hyperthermophilic archaeon Thermococcus sp. NA1.

Genomic analysis of a hyperthermophilic archaeon Thermococcus sp. NA1 revealed the presence of an 885-bp open reading frame encoding a protein of 295 amino acids with a calculated molecular mass of 32,981 Da. Analysis of the deduced amino acid sequence showed that amino acid residues important for catalytic activity and the metal binding ligands conserved in all of methionyl aminopeptidases (MetAP) were also conserved and belonged to type IIa MetAP. The protein, designated TNA1_MetAP (Thermococcus sp. NA1 MetAP), was cloned and expressed in Escherichia coli. The recombinant enzyme was a Mn(2+)-, Ni(2+)-, Fe(2+)-, or Co(2+)-dependent metallopeptidase. Optimal MetAP activity against L: -methionine p-nitroanilide (Met-pNA) (K (m) = 0.68 mM) occurred at pH 7.0 and 80 to 90 degrees C. The MetAP was very unstable compared to Pyrococcus furiosus MetAP, which was completely inactivated by heating at 80 degrees C for 5 min. It seemed likely that the cysteine residue (Cys53) played a critical role in regulating the thermostability of TNA1_MetAP.

Factors causing delay in discharge of elderly patients in an acute care hospital.

INTRODUCTION: Prolonged hospitalisation not only increases cost, it is also associated with other complications. Length of stay (LOS) is one of the indicators that reflect total cost of care during hospitalisation. So, it is of paramount importance to find out why elderly patients overstay in acute care hospitals and address these issues proactively. Since no local data is available, a study was planned to ascertain reasons why the discharging of elderly patients from hospital is delayed and whether these reasons are avoidable. MATERIALS AND METHODS: Long-stay patients were defined as those whose LOS had notably exceeded the average LOS for the Diagnosis Related Group (DRG), based on principal admitting diagnosis. A separate analysis showed that the specialty-specific long-stay marker for geriatric medicine was 28 days, so casenote review was done for all patients with LOS of more than 28 days who were discharged from geriatric medicine service of an acute care hospital during a 1-year study period. Information was collected on demographic profile, functional and cognitive status, past medical and social history, admitting medical diagnoses, discharge limiting and delaying factors. RESULTS: During the study period, 150 patients stayed over 28 days and 137 casenotes were available for review. The mean age of the patients was 84 years, 55.5% were female, 77.4% were Chinese, mean abbreviated mental test (AMT) score was 3 and mean modified Barthel's score was 11. The commonest primary diagnosis was sepsis followed by neurological problems, falls-related complication and cardiovascular diseases. The 2 most common discharge limiting factors (the final event which resulted in delay in discharge) were social issues (54, 39.4%) and sepsis (47, 34.3%). Of 47 patients with sepsis, 37 (78.7%) were nosocomial infection. Urinary tract infection and pneumonia were the 2 most common nosocomial infections. The 4 most common factors contributing to delayed discharge (various problems that surfaced throughout the hospital stay) were sepsis (94, 68.6%), deconditioning (65, 47.4%), social issues (52, 38.0%) and cardiovascular disorders (37, 27.0%). CONCLUSION: Elderly patients are more prone to hospitalisation-related complications like nosocomial infection and deconditioning leading to prolonged hospital stay. Early interventions can reduce these complications. Early identification of social issues and prompt discharge planning should be done to avoid delay in discharge.

Recent progress on biomass co-pyrolysis conversion into high-quality bio-oil.

Co-pyrolysis of biomass with abundantly available materials could be an economical method for production of bio-fuels. However, elimination of oxygenated compounds poses a considerable challenge. Catalytic co-pyrolysis is another potential technique for upgrading bio-oils for application as liquid fuels in standard engines. This technique promotes the production of high-quality bio-oil through acid catalyzed reduction of oxygenated compounds and mutagenic polyaromatic hydrocarbons. This work aims to review and summarize research progress on co-pyrolysis and catalytic co-pyrolysis, as well as their benefits on enhancement of bio-oils derived from biomass. This review focuses on the potential of plastic wastes and coal materials as co-feed in co-pyrolysis to produce valuable liquid fuel. This paper also proposes future directions for using this technique to obtain high yields of bio-oils.

Optimal timing for hepatitis C therapy in US patients eligible for liver transplantation: a cost-effectiveness analysis.

BACKGROUND: Recurrence of hepatitis C virus (HCV) following liver transplantation (LT) is universal for those with ongoing viraemia and is associated with higher rates of allograft failure and death. However, the optimal timing of HCV treatment for patients awaiting transplant remains unclear. AIM: To evaluate the comparative cost-effectiveness of treating HCV pre-LT vs. post-LT (pre-emptive or after HCV recurrence). METHODS: A Markov state-transition model was created to simulate the progression of a cohort of HCV-genotype 1 or 4 cirrhotic patients from the time of transplant listing until death. We then used this model to study the cost-effectiveness of ledipasvir-sofosbuvir (LDV/SOF) with ribavirin for 12 weeks, administered for three separate treatment strategies: (i) pre-LT; (ii) post-LT preemptively prior to HCV recurrence; or (iii) post-LT after HCV recurrence. RESULTS: In the base-case analysis using a median model for end-stage liver disease (MELD) score <25 at the time of transplant, we found that pre-LT treatment of HCV led to more QALYs for fewer dollars compared to other strategies. Analysis limited to living donor LT recipients revealed that pre-LT treatment was also the most cost-effective strategy. When the analysis was repeated for MELD ≥25, decompensated disease (Child-Pugh class B or C), and hepatocellular carcinoma cases, preemptive post-LT strategy was more cost-effective. CONCLUSIONS: Treatment of HCV prior to liver transplantation appears to be the most cost-effective strategy for patients with a MELD score <25. For patients with a MELD ≥25 or decompensated cirrhosis, preemptive post-liver transplantation treatment before HCV recurrence is the most cost-effective strategy.

Outcomes of standard and tailored anti-tuberculosis regimens in patients with tuberculous pleural effusion.

BACKGROUND: In an era of increasing concerns about drug resistance, there are limited data on treatment outcomes and recurrence rates after standard short-course anti-tuberculosis treatment in patients with culture-negative tuberculous pleural effusion (TPE). OBJECTIVE: To compare treatment outcomes and recurrence rates between a standard anti-tuberculosis regimen with negative culture and unavailable drug susceptibility testing (DST) data, and a tailored anti-tuberculosis regimen based on individual DST data. DESIGN: We analysed the data of all patients with TPE from the TB registry database at Kyungpook National University Hospital, South Korea, during 2008-2012. The study population was divided into two groups according to regimen. RESULTS: Standard and tailored anti-tuberculosis regimens were administered to respectively 124 and 146 patients with TPE. Drug resistance was detected in 10% of patients with TPE, about a quarter of whom were multidrug-resistant. The treatment completion rate was not significantly different between the two groups (91% vs. 93%). During a median 20-month follow-up, the recurrence rate was also similar in both groups (1% vs.1%). CONCLUSIONS: Despite limited statistical power, these preliminary results support the hypothesis that immunocompetent patients with culture-negative TPE can be appropriately managed with a standard short-course anti-tuberculosis regimen, even in this era of increasing concerns about drug resistance.

Entecavir safety and effectiveness in a national cohort of treatment-naïve chronic hepatitis B patients in the US - the ENUMERATE study.

BACKGROUND: Entecavir (ETV) has been shown to be safe and efficacious in randomised controlled trials in highly selected patients with hepatitis B virus (HBV) infection. AIM: To determine the safety and effectiveness of ETV in 'real-world' HBV patients in the United States (US). METHODS: Treatment-naïve HBV patients ≥18 years old who received ETV for ≥12 months between 2005 and 2013 were included in a retrospective, cohort study. Rates of ALT normalisation, undetectable HBV DNA, HBeAg and HBsAg loss/seroconversion, adverse events (AE) and clinical outcomes were evaluated. RESULTS: Of 841 patients, 658 [65% male, 83% Asian; median age 47 years] met the inclusion criteria. 36% were HBeAg+ and 9.3% cirrhotic. 89% had abnormal ALT. Baseline median HBV DNA was 5.8 log 10 IU/mL. Median duration of ETV treatment was 4 years. Rates of ALT normalisation at 1, 3 and 5 years were 37.2%, 48.7% and 56.2% in HBeAg+ and 39.6%, 46.8% and 55.6% in HBeAg- patients. HBV DNA was undetectable at 1, 3 and 5 years in 34.6%, 64.7% and 84.6% in HBeAg+ patients, and 81.9%, 90.3% and 96.2% in HBeAg patients. Five-year cumulative probability of HBeAg loss and seroconversion was 46% and 33.7% and HBsAg loss was 4.6%. ETV was discontinued due to adverse events in 1.2% of patients. Hepatic decompensation occurred in 0.8%, liver cancer in 2.7% and death in 0.6%. CONCLUSION: Entecavir treatment was safe in a large cohort of US patients, but ALT normalisation and hepatitis B virus DNA suppression rates were lower than previously reported in clinical trials.

Cloning and characterization of a bovine alpha interferon receptor.

A bovine interferon alpha receptor (BoIFN-alpha R1) cDNA, homologous to the human cDNA, was isolated. Transfection of the BoIFN-alpha R1 cDNA into monkey COS cells results in a large increase in high-affinity binding sites for human IFN-alpha A and IFN-alpha B. Covalent crosslinking of radiolabeled HuIFN-alpha A and -alpha B demonstrates that the complex of [32P]HuIFN with the BoIFN-alpha R1 protein (predicted mass, 61,375) expressed in COS cells migrates as a 140-150 kDa band.