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).

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.

Medicina Clínica, un nuevo rumbo / Medicina Clínica, un nuevo rumbo

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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.

Prospective evaluation of latent tuberculosis with interferon-gamma release assays in drug and alcohol abusers.

In vitro tests have been developed for the diagnosis of tuberculosis (TB) infection. The objective was to analyse latent TB infection in drug and alcohol abusers through two interferon-gamma techniques. One hundred and thirty-nine patients were admitted between February 2006 and May 2007. Mean age was 39.8 years [31% HIV positive]. The enzyme immunoassay (EIA) and enzyme-linked immunospot (ELISPOT) interferon-gamma assays were positive in 34% of patients with an agreement of 83% (kappa=0.63). Tuberculin skin test (TST) was positive in 29% of patients and the agreement of TST with EIA and ELISPOT interferon-gamma assays was 85% (kappa=0.62) and 83% (kappa=0.57), respectively. Almost 50% of patients with history of TB had a positive in vitro test. In conclusion, we observed a high prevalence of latent TB and good agreement between the new in vitro tests that otherwise may continue to be positive long after developing TB disease.

Cytopathogenicity and molecular subtyping of Legionella pneumophila environmental isolates from 17 hospitals.

The cytopathogenicity of 22 Legionella pneumophila isolates from 17 hospitals was determined by assessing the dose of bacteria necessary to produce 50% cytopathic effect (CPED50) in U937 human-derived macrophages. All isolates were able to infect and grow in macrophage-like cells (range log10 CPED50: 2.67-6.73 c.f.u./ml). Five groups were established and related to the serogroup, the number of PFGE patterns coexisting in the same hospital water distribution system, and the possible reporting of hospital-acquired Legionnaires' disease cases. L. pneumophila serogroup 1 isolates had the highest cytopathogenicity (P=0.003). Moreover, a trend to more cytopathogenic groups (groups 1-3) in hospitals with more than one PFGE pattern of L. pneumophila in the water distribution system (60% vs. 17%) and in hospitals reporting cases of hospital-acquired Legionnaires' disease (36.3% vs. 16.6%) was observed. We conclude that the cytopathogenicty of environmental L. pneumophila should be taken into account in evaluating the risk of a contaminated water reservoir in a hospital and hospital acquisition of Legionnaires' disease.

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.

Time on antiretroviral therapy is a protective factor for liver fibrosis in HIV and hepatitis C virus (HCV) co-infected patients.

To assess the factors associated with liver fibrosis in human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients eligible for anti-HCV therapy, we performed an observational, single-centred, cross-sectional study of 180 HIV/HCV co-infected patients who underwent liver biopsy between May 1998 and November 2001. A total of 126 patients with a known date of HCV infection were evaluated. Liver fibrosis was defined as a Knodell stage of fibrosis 1-4. The mean age was 36.7 (3.8) years, 81% were male and had a mean age of 20.5 (3.8) years at HCV infection. Mean CD4 cell count and plasma HIV-1 RNA load at the time of biopsy were 552 cell/mm3 (239) and 2.5 log10 (0.9), respectively; 118 patients had been on antiretroviral therapy (ART) for a median of 45 months (Q1-Q3: 21-75) and 84 on protease inhibitor for a median of 12.0 months (Q1-Q3: 0-29.5); 55 had an AIDS event or a CD4 cell count nadir < 200 cells/mm3 prior to biopsy. Median histological activity index was 6 and 27% had a Knodell stage of fibrosis 0. On the multivariate analysis time on ART (OR for 6 months extra: 0.954, 95% CI: 0.859-0.994), CD4 cell count at the time of liver biopsy (OR for 100 cells/mL increase: 0.740, 95% CI: 0.670-0.905), age at HCV infection acquisition (OR for 5 years extra: 2.594, 95% CI: 1.326-5.133) and alcohol intake (> 50 g/day) (OR: 2.73, 95% CI: 1.108-6.731) were associated with liver fibrosis. Hence ART should be a priority in HIV/HCV co-infected patients eligible for anti-HCV treatment as it is a protective factor for liver fibrosis.

Initiation, changes in use and effectiveness of highly active anti-retroviral therapy in a cohort of injecting drug users.

The prevalence of anti-retroviral therapy (ART) use over time and the incidence of AIDS in a cohort of HIV-seroconverting injecting drug users (IDUs) were assessed by means of a hospital-based study of IDUs with a well documented date of HIV infection. Use of ART and clinical endpoints were assessed by hospital records. Three calendar periods (before 1992, 1992-6 and 1997-2000) were defined as corresponding to modalities of ART available. Prevalence of ART usage in each calendar period, changes in medication and, hazard of AIDS in patients reaching the same duration of HIV infection at different calendar periods were analysed. In total, 132 IDUs with a median age of 23 years at seroconversion were followed up for 6.8 years (median) (range 0.2-15.7). At the end of the study, 58 patients (44%) had developed AIDS. Before the introduction of highly active anti-retroviral therapy (HAART) 12% of patients were on ART. Starting in 1997, an increasing proportion were receiving HAART with a prevalence of 39.5% by January 2000. Taking 1992-6 as the reference category the relative hazard of AIDS during 1997-2000 was 0.42 (95% CI, 0.1-1.1) (P = 0.09). A 40% penetration of HAART in a cohort of IDUs with known dates of seroconversion resulted in a 58 % reduction of the hazard of AIDS.

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.

[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.

Evaluación de la interpretación de la radiografía de tórax por los médicos de guardia en un hospital universitario / Evaluation of chest X-ray readings by emergency room physicians of a universitary hospital

FUNDAMENTO: Analizar si la interpretación sistemática de las radiografías de tórax en urgencias por un radiólogo obtendría mayor rendimiento diagnóstico y mejoraría los resultados asistenciales. MATERIAL Y MÉTODO: Estudio descriptivo de los ingresos de 3 meses, recogiéndose la interpretación de la radiografía de tórax del médico de guardia y, al día siguiente, la de un radiólogo. Se compararon los diagnósticos radiológicos de los dos y, posteriormente, se evaluó si los cambios hubiesen modificado el tratamiento. RESULTADOS: La discordancia entre el médico de guardia y el radiólogo es del 13,7 por ciento. De los 29 casos discordantes, el radiólogo concordaba con el informe de alta en 19 (65,5 por ciento), y de éstos en ocho habría habido un cambio en el tratamiento, siendo en siete de ellos de valor positivo, de acuerdo con el diagnóstico final. Las diferencias entre los dos médicos no eran significativas. CONCLUSIÓN: Parece existir una tendencia a un mayor rendimiento diagnóstico de la radiografía de tórax en urgencias con la participación del radiólogo en su interpretación (AU)

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.

Mortality of HIV-positive and HIV-negative heroin abusers as a function of duration of injecting drug use.

OBJECTIVE: To determine the incidence of mortality of injecting drug users as a function of the duration of injecting drugs and HIV status, and to assess how these effects vary according to age at initiation and calendar period (before and after 1992). METHODS AND DESIGN: Cohort of 376 intravenous heroin users admitted to detoxification between February 1987 and January 1990. SETTING: Patients referred from outpatient clinics of metropolitan Barcelona. Duration and characteristics of drug use were determined by interviews. Blood samples were collected during admission and analyzed for HIV, CD4+ cell count and different biologic parameters. Assessment of vital status and causes of death were obtained by hospital charts, death certificates, and autopsies. RESULTS: The study population consisted of 299 men and 77 women, whose mean age at entry was 26 years, mean duration of injecting drug use before admission 6.1 years; HIV seroprevalence at entry 70.2%. By the end of the follow-up (median 5.6 years), 21.8% of individuals had died (26.6% in HIV-positive, and 10.7% in HIV-negative injecting users). Based on Kaplan-Meier estimates, 10%, 20%, and 30% of HIV negative patients died by 8.7, 11.3 and 14.3 years, respectively, after initiating injecting drugs. The corresponding survival times for the seropositives were substantially lower: 6.6, 8.5, and 11.6 years, respectively. Overall, the survival time was significantly (p < .05) decreased by 22% in HIV-positive injecting drug users. Older age at initiation of injecting drug use was significantly (p < .05) associated with mortality in HIV-positive heroin users but it showed the opposite direction among HIV-negative people. Death rates in HIV-positive patients of the same duration of drug use were similar in periods before and after 1992 (relative hazard (RH) = 0.97; 95% confidence interval: 0.58-1.61). Although not statistically significant, the hazard of death in HIV-negative injecting drug users was substantially lower after 1992 (RH = 0.59). CONCLUSIONS: Before introduction of potent antiretroviral therapies, HIV infection further increased rates of mortality that had already been heightened by injecting drug use. Furthermore, HIV infection modifies the effect of age at initiation and eliminates the seemingly downward trend of mortality in HIV-negative people.