Impact of age on viral kinetics of peginterferon alfa-2a/ribavirin in chronic hepatitis C: final analysis from the PROPHESYS cohort.

The population of patients with chronic hepatitis C viral infection is ageing; however, elderly, hepatitis C-infected patients are understudied and less frequently treated. This subanalysis of data from the multinational PROPHESYS study examined associations between age (≤65 vs >65 years), on-treatment virological response and sustained virological response (SVR) in patients treated with peginterferon alfa-2a (40KD)/ribavirin in accordance with local licences. PROPHESYS comprised three cohorts studied in 19 countries according to country-specific legal and regulatory requirements. This subanalysis includes treatment-naive HCV mono-infected patients assigned to receive peginterferon alfa-2a (40KD)/ribavirin, with 6276 individuals aged ≤65 years and 349 aged >65 years. Rapid virological response (RVR) rates by Week 4 were consistently lower in older genotype (G) 1 (21.6% vs 27.2% in younger patients), G2 (80.7% vs 85.1%) and G3 (60.0% vs 74.2%) patients. SVR rates were significantly lower (29.8% vs 43.0%) and relapse rates significantly higher (43.1% vs 26.7%) in older G1 patients (P = 0.0002 vs ≤65 years). In contrast, SVR and relapse rates were similar in G2 and G3 patients regardless of age. The positive predictive value of RVR for SVR was comparable in older and younger G1 patients (66.7% vs 68.6%, respectively) and higher in older G2 (80.7% vs 75.6%) and G3 (77.8% vs 66.8%) patients. Virological response rates are generally lower in elderly CHC patients, and RVR is a reliable positive predictor of SVR in patients >65 years.

Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa-2a combination therapy for chronic hepatitis B.

BACKGROUND: In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy. AIM: To identify baseline and on-treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks. METHODS: A secondary analysis of data from an open-label study where patients were randomised to TDF (300 mg/day, oral) plus PEG-IFN (PI, 180 µg/week, subcutaneous) for 48 weeks (TDF/PI-48w); TDF plus PEG-IFN for 16 weeks, TDF for 32 weeks (TDF/PI-16w+TDF-32w); TDF for 120 weeks (TDF-120w) or PEG-IFN for 48 weeks (PI-48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72. RESULTS: Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI-48w group (6.5%) than in the TDF/PI-16w+TDF-32w (0.5%), TDF-120w (0%) and PI-48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI-48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72. CONCLUSIONS: HBsAg decline at Week 24 of TDF plus PEG-IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.

[Fungal endogenous endophthalmitis--case report]. / Endoftalmita endogena fungica--caz clinic--.

This paper presents a particular case of endogenous candida endophthalmitis, at a patient with lots of risk factors; the correct diagnosis was relatively late; it had been surgically solved by posterior vitrectomy.

Diagnosis Performance of Different MR Imaging Signs of Cirrhosis: the Caudate to Right Lobe Ratio, the Posterior Right Hepatic Notch, and the Expanded Gallbladder Fossa.

Background & Aims The purpose of the study is to evaluate the accuracy of the C/RL, RPN, and EGF in diagnosing cirrhosis. Methods The study population included 95 cirrhotic patients in the cirrhosis group (56 men, 39 women, age range 14-76;mean age 52.3) and 57 subjects in the control group (26 men, 31 women, age range 18-83;mean age 51). All MR examinations were performed by using the same protocol. Two radiologists independently assessed data sets in two different reading sessions. The sensitivity, specificity, and accuracy and the relative risk of the signs in diagnosing cirrhosis were calculated. The diagnosis accuracy of the C/RL sign was calculated using the ROC curve. The statistical significance of any difference of each sign between different classes of cirrhosis was also calculated. Results The interobserver agreement between the readers was excellent (κ≥ 0.81;95% CI:0.92, 1.0). There was a significant statistical difference of the diagnostic value of C/RL, RPN, and EGF between cirrhotic patients and control group (p<0.001). The sensitivity, specificity, and accuracy of C/RL were 72%, 87%, and 78%; 67%, 87%, and 75% for RPN; and 49%, 91%, and 65% for EGF. C/RL (OR=18.95) and RPN (OR=14.74) showed a higher risk for cirrhosis compared to EGF (OR=14.74). There was a statistical significance difference between C/RL and EGF (p=0.002) and between RPN and EGF for Child A class of cirrhosis (p-0.037). Conclusion The C/RL and RPN have similar performance regarding the diagnosis of cirrhosis having a higher diagnostic performance compared to EGF in cirrhosis.

[Control of the effectiveness of antibiotic therapy by determining the antibacterial activity of the blood and cerebrospinal fluid]. / Practica controlului eficientei antibioticoterapiei prin determinarea actiunii antibacteriene a serului si lichidului cefalorahidian.

Determination of the antibacterial action of serum and the cerebrospinal fluid (CSF) is an excellent method for controlling the efficiency of antibioticotherapy in severe bacterial infections such as septicemia, endocarditis, meningitis. The author studied comparatively two methods for determining the antibacterial action of serum and CSF, namely dilution of the standard inoculum and diffusimetric methods. There was satisfactory agreement between the two methods. Hence, diffusimetry, a simple readily performed method, may be considered as an orientative test of the greatest utility, available for any of the lesser clinical laboratories.

Possibilities of perfecting antimicrobial therapy. Dynamics of penicillin G concentrations in the cerebro-spinal fluid in purulent meningitis.

In 43 adult patients with purulent meningitis receiving daily doses of 1-4,000,000 IU penicillin G i.v. in bolus, determinations were made, 1-6 hrs after administration, in 153 samples of cerebrospinal fluid (CSF), to ascertain the concentrations of penicillin that have reached the CSF. After 1 hour maximum levels of penicillin were noted, exceeding by far the meningococcus and pneumococcus minimum inhibitory concentration (MIC). Generally, high penicillin concentrations persisted in the CSF, in most of the cases at least for the following 6 hours. The advantages of using penicillin G i.v. in doses of 1-3,000,000 IU in bolus at 12 hour intervals are discussed. All the 36 patients with meningococcal meningitis and 3 of the 5 with pneumococcal meningitis recovered with this therapeutic scheme, under daily control of the CSF.

[The etiological profile of the pulmonary manifestations in AIDS patients (studies of 65 cases recorded in Romania up to 1 March 1993)]. / Profilul etiologic al manifestarilor pulmonare la bolnavii de SIDA (studii pe 65 cazuri înregistrate în România pâna la 1 III 1993).

HIV infection and its final form as AIDS were ignored by the public opinion in Romania till 1990. Nowadays it is real fact in our country. Out of total number of 2235 AIDS cases declared till March 1st 1993 by the Ministry of Health only 134 were adult persons. The study concerns 65 cases of AIDS in adults in order to find out the lung symptoms proportion as etiologic features, to settle the ways of transmission of HIV infection and to warn the romanian pneumologists on this problem. The study shows that in 56.9% of total cases, lung symptoms were noted and in 49.2% the lung disease revealed the AIDS. Out of the total number of 65 cases, 24.6% showed tuberculosis as a first disease, 12.4% lung pneumocystosis, 7.76 Kaposi syndrome with lung expression and 4.5% other pneumopathies.

Q fever urban cases in Romania.

Q fever urban sporadic cases in Romania in the 1981-87 period are reviewed as concerns their incidence, seasonality and epidemiological data. Urban cases represented 76.8% as against 23.2% rural cases from the 134 Q fever sporadic cases detected in this period. Cases were distributed throughout all months with peaks during April (18.4% of cases) and June (19.4%). Infections were not related to contact with livestock or domestic birds or with raw milk drinking. Cases could not be identified as Q fever occupational ones. 36.7% of patients were working in nonalimentary industry and only 12.6% were involved in meat industry, veterinary or human medical practices. New studies concerning unusual sources of urban infection such as dogs, cats or urban street pigeons are emphasized.

Preliminary investigations on the diagnostic value of passive hemagglutination and complement fixation tests in infections with Mycoplasma pneumoniae.

In order to evaluate the efficiency of passive hemagglutination (PHA) and complement fixation (CF) tests for the diagnosis of M. pneumoniae infections, 144 serum samples--out of which 81 from patients with respiratory and cutaneous infections and 63 from subjects with other diseases (controls)--were comparatively investigated by the two methods. The PHA test made evident a positivity index of 65% in the case of mixed pneumonias, as against 17% in controls, while the results obtained by CF were almost identical in the two groups investigated. The high specificity and sensitivity of the PHA reaction recommend this method for the diagnosis of acute M. pneumoniae infections.

Medium-long incubation posttransfusional hepatitis (a possible immunological implication).

Icteric hepatitis which developed in the first 6 months after blood transfusion was studied in 159 cases. One fourth of these (39) occurred within a period of only 15 days: between the 30th and 45th day after transfusion. So, their incubation period was longer than that of short incubation hepatitis (type A), and shorter than that of long incubation hepatitis (type B). In these cases the incidence of HBs antibodies was more than 10 times greater than in hepatitis with long incubation, and the incidence of HBs antigen was approximately the same as in the healthy control group. This fact suggests the involvement of a special factor in their appearance, probably an immunologic (or of other nature) process giving rise to antigen-antibody complexes in the HB ag-ab system.

Value of serological tests in the diagnosis of viral acute respiratory infections in adults.

The dynamics of the antibody response to influenza viruses A (H1N1), A (H3N2) and B, to parainfluenza viruses 1, 2, 3, to adenoviruses and respiratory syncytial virus was studied in paired serum samples collected from 110 patients hospitalized with acute respiratory infections (ARI) and in 40 patients suffering from other diseases. Rises in serum antibody titers to 1--5 of the above mentioned antigens were detected in many of the patients of both groups. The fact is most likely due to the presence of some epidemiologically and clinically uncharacteristic viral ARI (influenza included); simultaneous or successive infections with influenza virus and different other viruses were very frequent. A greater efficiency of the etiological diagnosis of viral ARI can be achieved only by the association of epidemiological and clinical criteria with serological data, the visualization of viral antigens and virus isolation.

Passive hemagglutination and complement fixation reactions in the early diagnosis of Mycoplasma pneumoniae infections.

Complement fixation (CF) and passive hemagglutination (PHA) tests (the latter with a M. pneumoniae antigen coupled by glutaraldehyde onto red blood cells) were performed in 263 patients with various infectious diseases (mostly in the 1st and 2nd week after onset) and non-infectious ones. CF reaction proved to be inappropriate for the early etiological diagnosis of mycoplasma infections, since the high titers were distributed undifferentially among the various patient groups and many sera (38%) showed anticomplementary activity. A PHA titer of at least 1/128 (preferably of 1/512) points to the presence of a M. pneumoniae infection, especially if clinical, radiological and laboratory data suggest a nonbacterial or mixed pneumonia. The diagnosis is often early enough to orientate the etiological therapy towards macrolides and tetracyclines. The PHA reaction recommended is specific, sensitive, reproducible and easy to perform.