Hyaluronic acid, transforming growth factor-beta1 and hepatic fibrosis in patients with chronic hepatitis C virus and human immunodeficiency virus co-infection.

Chronic hepatitis C virus (HCV) infection follows an accelerated course in patients co-infected with human immunodeficiency virus (HIV); establishing the extent of liver fibrosis is crucial for disease staging and determining treatment strategy in these patients. The utility of noninvasive markers of fibrosis as alternatives to liver biopsy has not been well-studied in these patients. We evaluated the predictive value of serum transforming growth factor-beta1 (TGF-beta1) and hyaluronic acid (HA) levels for determining the extent of liver fibrosis. Liver biopsies and blood samples were collected from 69 consecutive patients (74% male; median age, 41 years) between May 2005 and November 2006. Serum TGF-beta1 and HA were analysed using commercial kits. Aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase levels were elevated in 81%, 70% and 60% of patients, respectively. Fifty-three patients (90%) were on highly active antiretroviral therapy and the median CD4-positive cell count was 422 cells/microL. The extent of fibrosis according to Scheuer's scoring was 32% F0 (no fibrosis), 16.5% F1, 16.5% F2, 26% F3 and 7% F4 (cirrhosis). Mean serum TGF-beta1 was 36.1 +/- 14.4 ng/mL; mean serum HA was 75.2 +/- 85.0 microg/L. Serum HA was positively associated and significantly correlated with the stage of fibrosis (r = 0.56; P < 0.05). The area under the curve for discriminating mild (F0-F2) from significant (F3-F4) fibrosis in receiver operating analysis using HA was 0.83 (sensitivity, 87%; specificity, 70%). These data suggest that HA is clinically useful for predicting liver fibrosis and cirrhosis in patients co-infected with HCV/HIV. However, serum TGF-beta1 was not predictive of histological damage in co-infected individuals treated with HAART.

Clinical utility of HIV-1 genotyping and expert advice: the Havana trial.

OBJECTIVE: To determine whether HIV-1 genotyping and expert advice add additional short-term virologic benefit in guiding antiretroviral changes in HIV+ drug-experienced patients. DESIGN: A two factorial (genotyping and expert advice), randomized, open label, multi-center trial. The patients were stratified according to the number of treatment failures. PATIENTS AND METHODS: HIV-1 infected patients on stable antiretroviral therapy who presented virological failure were included into the study. Genotypic testing was performed by using TrueGene HIV Genotyping kit and the results were interpreted by a software package (RetroGram, version 1.0). An expert advisory committee suggested the new therapeutic approach based on clinical information alone or on clinical information plus HIV-1 genotyping results. Plasma HIV-1 RNA load, CD4+ cell count and adverse events were recorded at baseline and every 12 weeks. RESULTS: A total of 326 patients were included. The baseline CD4+ cell count and plasma HIV-1 RNA were 387 (+/- 224) x 10(6) cells/l and 4 (+/- 1) log(10) respectively. The proportion of patients with plasma HIV-1 RNA < 400 copies/ml at 24 weeks differed between genotyping and no genotyping arms (48.5 and 36.2%, P < 0.05). Factors associated with a higher probability of plasma HIV-1 RNA < 400 copies/ml were HIV-1 genotyping [odds ratio (OR), 1.7; 95% confidence interval (CI), 1.1-2.8; P = 0.016] and the expert advice in patients failing to a second-line antiretroviral therapy (OR, 3.2; 95% CI, 1.2-8.3; P = 0.016). CONCLUSIONS: HIV-1 genotyping interpreted by a software package improves the virological outcome when it is added to the clinical information as a basis for decisions on changing antiretroviral therapy. The expert advice also showed virologic benefit in the second failure group.

Infusion phlebitis in patients with acute pneumonia: a prospective study.

STUDY OBJECTIVES: To prospectively assess the relative risk for phlebitis in a series of consecutive patients with pneumonia and to identify risk factors that predict an increased risk for phlebitis. SETTING: Internal medicine department of a tertiary teaching hospital. PATIENTS: Seven hundred sixty-six consecutive patients with acute pneumonia receiving IV therapy. INTERVENTIONS: Only the first catheter was taken into account. There were 308 short lines (a 51-mm, 18-gauge Teflon catheter); 307 midsized lines (a 28-cm, 16-gauge polyvinyl chloride catheter); and 151 long lines (71-cm, 14-gauge plain polyurethane catheter). Eighteen variables were prospectively evaluated in an open, nonrandomized study for their contribution to the occurrence of phlebitis. RESULTS: The overall phlebitis rate was 39%. Phlebitis developed in 53% of patients with short lines, in 41% of patients with midsized lines, and in 10% of patients with long lines, and these catheters remained in place an average (+/- SD) of 3.0+/-2.4 days, 4.6+/-3.4 days, and 7.8+/-6.6 days, respectively. The variables that influenced the development of phlebitis, as determined by multivariate analysis, were the following: type of catheter; blood hemoglobin levels; and IV therapy with either corticosteroids or erythromycin. CONCLUSIONS: According to our data, when the use of a catheter is expected to be required for < or = 36 h, a short line can be used. If a longer duration is expected, a longer line is warranted. Ours is the first study in which the relationship between blood hemoglobin levels and phlebitis has been reported. Because the use of intravascular devices is increasingly common, a more complete knowledge of the factors that influence their acceptance has become essential.

Environmental cultures and hospital-acquired Legionnaires' disease: a 5-year prospective study in 20 hospitals in Catalonia, Spain.

OBJECTIVE: To determine whether environmental cultures for Legionella increase the index of suspicion for legionnaires' disease (LD). DESIGN: Five-year prospective study. SETTING: Twenty hospitals in Catalonia, Spain. METHODS: From 1994 to 1996, the potable water systems of 20 hospitals in Catalonia were tested for Legionella. Cases of hospital-acquired LD and availability of an "in-house" Legionella test in the previous 4 years were assessed. After the hospitals were informed of the results of their water cultures, a prospective 5-year-study was conducted focusing on the detection of new cases of nosocomial legionellosis and the availability and use of Legionella testing. RESULTS: Before environmental cultures were started, only one hospital had conducted active surveillance of hospital-acquired pneumonia and used Legionella tests including Legionella urinary antigen in all pneumonia cases. Only one other hospital had used the latter test at all. In six hospitals, Legionella tests had been completely unavailable. Cases of nosocomial LD had been diagnosed in the previous 4 years in only two hospitals. During prospective surveillance, 12 hospitals (60%) used Legionella urinary antigen testing in house and 11 (55%) found cases of nosocomial legionellosis, representing 64.7% (11 of 17) of those with positive water cultures. Hospitals with negative water cultures did not find nosocomial LD. CONCLUSIONS: The environmental study increased the index of suspicion for nosocomial LD. The number of cases of nosocomial LD increased significantly during the prospective follow-up period, and most hospitals began using the Legionella urinary antigen test in their laboratories.

Presence and chromosomal subtyping of Legionella species in potable water systems in 20 hospitals of Catalonia, Spain.

OBJECTIVE: To investigate the presence and clonal distribution of Legionella species in the water supply of 20 hospitals in Catalonia, Spain. SETTING: 20 hospitals in Catalonia, an area of 32,000 km2, located in northeast Spain. METHODS: Environmental cultures of 186 points of potable water supply and 10 cooling towers were performed for the presence of Legionella species. Following filtration and acid treatment, the samples were seeded in selective MWY (modified Wadowsky Yee)-buffered charcoal yeast extract-alpha agar. All isolates obtained were characterized microbiologically and genotyped by SfiI pulsed-field gel electrophoresis (PFGE). RESULTS: 73 of 196 water samples, representing 17 of the 20 hospitals included in the study, were positive for Legionella pneumophila (serogroups 1, 2-14, or both). The degree of contamination ranged from 200 to 74,250 colony-forming units/L. Twenty-five chromosomal DNA subtypes were detected by PFGE. A single DNA subtype was identified in 10 hospitals, 2 DNA subtypes were observed in 6 hospitals, and 1 hospital exhibited 3 different DNA subtypes. Each hospital had its own Legionella DNA subtype, which was not shared with any other hospitals. CONCLUSIONS: Legionella was present in the water of most of the hospitals studied; each such hospital had a unique, dominant chromosomal DNA subtype. The verification of several genomic DNA restriction profiles in such a small geographic area demonstrates the great genetic diversity of Legionella in the aquatic environment.

[Assessment of thoracic X-ray readings by emergency room physicians at a university hospital]. / Evaluación de la interpretación de la radiografía de tórax por los médicos de guardia en un hospital universitario.

BACKGROUND: We aimed to find out whether systematic reading of chest radiography (CRx) by radiologists in the emergency unit might lead to a higher diagnostic efficiency and improve health care. MATERIAL AND METHOD: Descriptive study of consecutive admissions during 3 months in an internal medicine department. We registered the CRx interpretation by the emergency unit physician first, and a radiologist the next day. In cases with different interpretations, we assessed whether these differences would have modified the treatment. RESULTS: The overall disagreement between the emergency room physician and the radiologist was 13.7%. In 19 of 29 cases with different readings, the radiologist interpretation was in agreement with the final diagnosis. In 7 of these 19 cases, the radiologist reading of CRx would have led to a positive change of treatment. However, differences between both physicians were not statistically significant. CONCLUSIONS: There seems to be a higher diagnostic efficiency when the emergency room physician interpretation of CRx is complemented by a radiologist.

[Tumor necrosis factor-alpha in human immunodeficiency virus infection]. / El factor de necrosis tumoral alfa en la infección por el virus de la immunodeficiencia humana.

BACKGROUND: The aim of the present was to determine the levels of the tumor necrosis factor (TNF)-alpha in patients with HIV infection to study the relationship with the concentration of triglycerides (TG), CD4 lymphocyte count and clinical diagnosis. METHODS: Seventy-eight HIV-infected patients (58 males, 20 females); mean age 32 years presenting different clinical situations were studied. TNF, TG, CD4 lymphocyte count, and clinical diagnosis at the time of the study were analyzed. RESULTS: The mean TNF values in the sample was 25.5 x 10(-3) pg/l with a confidence interval of 95% (Cl 95%), 16.6 x 10(-3) pg/l to 34.4 x 10(-3) pg/l with a trend to being higher in the group with less than 200 x 10(6) CD4/l (Cl 95%: 18.6 x 10(-3) pg/l-44.3 x 10(-3) pg/l). Mean TG values in the sample were 2.02 milligrams (Cl 95%: 1.72 milligrams-2.31 milligrams) being significantly higher in the group with less than 200 x 10(6) CD4/l (X = 2.35 +/- 1.32 milligrams; p < 0.005). TNF concentrations were found to be significantly higher in the group with acute infection (Cl 95%: 27 x 10(-3) pg/l-69 x 10(-3) pg/l) with respect to the group without infection at the time of the study (Cl 95% 7 x 10(-3) pg/l-19 x 10(-3) pg/l). The correlation coefficient between TNF and TG was r = 0.34 (p = 0.01). CONCLUSIONS: Both the tumor necrosis factor and triglycerides are high in patients with HIV infection and CD4 lower than 200 x 10(6)/l. The correlation between tumor necrosis factor and triglyceride concentrations is positive and significant. The increase in the former is more important when there is concomitant infection and could be considered as a marker of opportunistic infection.

[Dyslipemia and HIV-1 infection in intravenous drug addicts]. / Dislipemia e infección por VIH-1 en adictos a drogas intravenosas.

BACKGROUND: It has been demonstrated that hypertriglyceridemia and hypocholesterolemia are frequent signs in homosexual patients with AIDS. Lipid abnormalities of the intravenous drug addict (IVDA) however, and its relation with infection by the human immunodeficiency virus (HIV) have not been sufficiently studied. METHODS: Four hundred thirty-five consecutive patients attended for infectious complications or for carrying out detoxication treatment were studied. Demographic (age, sex), anthropometric (weight, height), use of intravenous drugs (principal drug used, time of addiction) and analytic data (HIV-1 antibodies, total lymphocytes, CD4+ lymphocytes, serum albumin, total cholesterol, plasma triglycerides and transferrinemia) were collected. RESULTS: The age of the patients was found to be between 15-44 years of age. Ninety-five percent were heroin addicts with a time of addiction greater than 4 years. Those who were HIV-1 positive had been drug users for a longer period of time (p < 0.01), had less weight (p < 0.01), lower albuminemia (p < 0.05) and cholesterolemia (p < 0.01), as well as a lower number of CD4+ lymphocytes (p < 0.01). No differences were observed with regard to age, transferrinemia and plasma triglyceride concentration. The prevalence of hypertriglyceridemia (> 1.97 mmol/l; 175 mg/dl) was of 18% for the IVDA with HIV-1 infection and 23% for seronegative individuals (p = 0.3). Hypercholesterolemia was significantly more prevalent in HIV-1 positive individuals (20%) than in the seronegative subjects (9%) (p < 0.01). In the HIV-1 positive patients, most of whom where asymptomatic, a decrease in total cholesterol and an increase in plasma triglycerides was observed according to the decrease in the number of CD4+ lymphocytes. CONCLUSIONS: Infection by the human immunodeficiency virus is accompanied by an increase in plasma triglycerides and a decrease of total cholesterol in relation with the alteration of cellular immunity. However, heroin addicts present some differential characteristics similar to those of chronic alcoholics, poor diet, anorexia induced by opioids, autoimmunity phenomena and recurrent infections throughout drug addiction which may justify lipid abnormalities of multifactorial origin.

[Wegener's granulomatosis: a report of 6 patients]. / Granulomatosis de Wegener: descripción de 6 pacientes.

The clinical and analytical manifestations and the evaluation of 6 patients diagnosed with Wegener's granulomatosis (WG) in the Germans Trias i Pujol Hospital between 1986-1990 are described. The most frequent clinical manifestation found were general and respiratory symptoms. Three patients presented an alteration in renal function and urinary sedimentation. Antibodies against the cytoplasm of the neutrophils (ANCA) detected by indirect immunofluorescence (IIF) were positive in 4 patients. All the patients underwent initial complete remission with immunodepressor treatment and one presented relapse of the disease at 19 months of diagnosis. Complications were: opportunistic infections obliging discontinuation of treatment in one patient, distal necrosis of the fingers requiring amputation in another patient and massive atelectasis of the right lung requiring pneumonectomy in a third patient.

[Diagnostic approach to neoplasms at an internal medicine service]. / Análisis de la conducta diagnóstica de las neoplasias en un servicio de medicina interna.

BACKGROUND: The aim of this study was to investigate the diagnostic behavior of different members of a department of internal medicine towards some neoplasms, analyzing the study times, reasons for suspicion and the number of tests performed and their results. PATIENTS AND METHODS: A retrospective review of the clinical histories of the patients admitted from January 1, 1992 to June 30, 1994 whose diagnosis was a new neoplasm of the digestive tract, lung cancer, cancer of unknown origin or lymphoma was carried out. The total diagnostic study time and the different partial times were measured and confirmed. The causes leading to suspicion of the neoplasms were also analyzed by groups, and finally the efficacy of the different diagnostic tests; either non invasive, oriented at the decision of the definitive test, or invasive (biopsies and fine needle aspiration puncture). RESULTS: The median total study time was 13 days with no differences between the groups. The median time until clinical suspicion was 0 days (interquartile range 0-2), being significantly greater in the digestive neoplasms. Less than half of the total study time corresponded to the clinical work itself (5 vs. 8 days). Suspicion of neoplasms in 49% of the cases arose from radiographic alteration and in 30% from clinical alterations. With regards to diagnostic tests, the value of thorax X-ray as the first exploration, mainly in the lung neoplasms (82.5% of the radiographies showed alterations), the elevated efficacy of computerized tomography, among the non invasive tests and fine needle aspiration puncture among the invasive tests were of note. Definitive diagnosis was achieved in 62% of the cases by biopsy and in 31% by fine needle aspiration puncture. CONCLUSIONS: Not all the time spent in achieving diagnosis of neoplasms is attributable to clinical work, although this may be shortened. To do so, a faster and more adequate use of the tests of greater performance (thorax X-ray, computerized tomography and fine needle aspiration puncture) should be used and performed with greater coordination and cooperation among the clinical technicians and physicians of the different departments.

[Rates of human immunodeficiency virus (HIV) infection in intravenous drug addicts from the Barcelona area, according to sex and age of drug consumption onset]. / Tasas de infección por el virus de la inmunodeficiencia humana (VIH) en drogadictos intravenosos del área de Barcelona, según sexo y edad de inicio en el consumo.

BACKGROUND: The differences in the rates of HIV infection in intravenous drug addicts according to the age of onset of drug consumption, sex and length of intake were evaluated. METHODS: The study sample was made up of 650 intravenous drug addicts (535 males and 115 females) admitted to a Hospital Detoxication Unit over 7 years (1987-1993). Of all these patients HIV serology and a questionnaire related to sociodemographic variables and drug consumption (age, sex, year of onset of intravenous drug intake, length of addiction and year of admission) were obtained. RESULTS: The rate of HIV infection for any length of addiction was higher in females than in males with this difference being significant for a length of addiction of less than 24 months (p = 0.03). The greater the age of onset in the use of intravenous drugs the lower the rate of HIV infection (p < 0.0001). In addiction times of less than 24 months the subjects who began drug consumption at an earlier age than the mean (19 years) presented significantly higher HIV infection rates (p = 0.04). CONCLUSIONS: Among the intravenous drug consumers in the area of Barcelona, Spain subgroups may be found: those who enter the consumption of intravenous drugs early and women, demonstrating high rates of HIV seroprevalence from the onset of their addiction.

[Immunoglobulin A and human immunodeficiency virus type 1 infection in parenteral drug abuse addicts]. / Inmunoglobulina A e infección por el virus de la inmunodeficiencia humana tipo 1 en adictos a drogas por vía parenteral.

BACKGROUND: To evaluate the usefulness of serum immunoglobulin A (IgA) as a prognostic marker of human immunodeficiency virus type 1 (HIV-1) in parenteral drug abusers (PDA). METHODS: The serum IgA levels and HIV-1 antibodies were assessed in 374 PDAs admitted for infective diseases or for treatment of addiction. RESULTS: The prevalence of HIV infection was 70%; the frequency of serum IgA above the upper normal limit (440 mg/dl) was 8% in seronegative and 4% in seropositive subjects (NS). The IgA levels in the 274 seropositive subjects, classified for infective stages, were significantly higher in those fulfilling the criteria for acquired immunodeficiency syndrome (AIDS) or AIDS related complex (group IV) than in asymptomatic subjects (group II) or in those with generalized lymphadenopathy (group III) (p less than 0.01). CONCLUSIONS: Serum IgA levels in PDAs with HIV infection may be a useful marker of progression to AIDS.

Estimated liver fibrosis and its impact on all-cause mortality of HCV-monoinfected and HCV/HIV-coinfected drug users.

UNLABELLED: Progression of liver fibrosis is associated with the risk of cirrhosis and end-stage liver disease. We aimed to evaluate fibrosis of the liver using three non-invasive indexes (FIB-4, Forns, and Pohl score) and its association with mortality of HCV-monoinfected and HCV/HIV-coinfected drug users. PATIENTS AND METHODS: longitudinal study in patients admitted to substance abuse treatment between 1994 and 2006. Socio-demographic data, drug use characteristics, blood samples for laboratory tests, and serology for HIV and hepatitis C virus infections were collected at admission. Patients were followed-up until December 2006 and mortality was ascertained through hospital charts and death certificates. RESULTS: Four hundred and ninety-seven patients were included (83.1% men); median age at admission was 31 years (IQR: 27-35). The main drugs of abuse were opiates (89.5%) and cocaine (8.3%). Thirty-two percent of patients reported daily alcohol consumption. The estimated prevalence of advanced liver fibrosis (ALF) was higher among HCV/HIV-coinfected patients (9.2% to 17.3% depending on the index analyzed) than among the HCV-monoinfected patients (3% to 3.5%). Odds ratio (OR) for ALF were 3.3 to 6.0 times higher in coinfected patients as compared to the HCV-monoinfected. After a median follow-up time of 7.7 years (IQR: 4.1-9.9 years), almost 20% of patients had died. The estimated ALF at admission was associated with an increased risk of death (RR 1.85 to 3.89 depending on the index). Among those with ALF, mortality rates were similar in HCV-monoinfected and HCV/HIV-coinfected patients, as determined by the FIB-4 and Forns indexes. CONCLUSIONS: Estimation of liver fibrosis using serum markers may help with clinical decisions to facilitate access to treatment of chronic hepatitis C in this population.

Effect of using reporting guidelines during peer review on quality of final manuscripts submitted to a biomedical journal: masked randomised trial.

OBJECTIVE: To investigate the effect of an additional review based on reporting guidelines such as STROBE and CONSORT on quality of manuscripts. DESIGN: Masked randomised trial. Population Original research manuscripts submitted to the Medicina Clínica journal from May 2008 to April 2009 and considered suitable for publication. CONTROL GROUP: conventional peer reviews alone. Intervention group: conventional review plus an additional review looking for missing items from reporting guidelines. Outcomes Manuscript quality, assessed with a 5 point Likert scale (primary: overall quality; secondary: average quality of specific items in paper). Main analysis compared groups as allocated, after adjustment for baseline factors (analysis of covariance); sensitivity analysis compared groups as reviewed. Adherence to reviewer suggestions assessed with Likert scale. RESULTS: Of 126 consecutive papers receiving conventional review, 34 were not suitable for publication. The remaining 92 papers were allocated to receive conventional reviews alone (n=41) or additional reviews (n=51). Four papers assigned to the conventional review group deviated from protocol; they received an additional review based on reporting guidelines. We saw an improvement in manuscript quality in favour of the additional review group (comparison as allocated, 0.25, 95% confidence interval -0.05 to 0.54; as reviewed, 0.33, 0.03 to 0.63). More papers with additional reviews than with conventional reviews alone improved from baseline (22 (43%) v eight (20%), difference 23.6% (3.2% to 44.0%), number needed to treat 4.2 (from 2.3 to 31.2), relative risk 2.21 (1.10 to 4.44)). Authors in the additional review group adhered more to suggestions from conventional reviews than to those from additional reviews (average increase 0.43 Likert points (0.19 to 0.67)). CONCLUSIONS: Additional reviews based on reporting guidelines improve manuscript quality, although the observed effect was smaller than hypothesised and not definitively demonstrated. Authors adhere more to suggestions from conventional reviews than to those from additional reviews, showing difficulties in adhering to high methodological standards at the latest research phases. To boost paper quality and impact, authors should be aware of future requirements of reporting guidelines at the very beginning of their study. Trial registration and protocol Although registries do not include trials of peer review, the protocol design was submitted to sponsored research projects (Instituto de Salud Carlos III, PI081903).