The authors show the results of an integrated model for risk management of tuberculosis in a sample of sheltered homeless in Rome. Tuberculin skin test (TST) was used for evaluating the prevalence of ...latent infection (LTBI). In TST positives, expectorate was collected and chest X-ray was achieved. Multiple logistic regression analysis was performed to investigate determinants of infection. Out of 288 recruited subjects, 259 returned for the TST reading; 45.56% were positive and referred to a specialized center; 70 accessed the health facility and completed the clinical pathway. The risk factors associated to LTBI were male gender (OR=3.72), age over 60 years (OR=3.59), immigrant status (OR=3.73), and obesity (OR=2.19). This approach, based on an integrated social network, guarantees high adherence to screening (89.93%), allowing patients testing positive for latent tuberculosis infection to be diagnosed and rapidly referred to a specialized center.
To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically ...aggressive non-Hodgkin's lymphoma (NHL).
We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease.
The rate of complete response was 68% in arm A and 76% in arm B (P = not significant NS). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P =.95), 5-year progression-free survival was 49% and 61% (P =.21), and 5-year relapse-free survival was 65% and 77% (P =.22), respectively.
Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.
Summary Background Five thematic working groups composed of Italian infectious disease experts and a group coordinator, supported by a scientific secretary, identified controversial issues in the ...field of severe healthcare-associated infections caused by multidrug-resistant organisms. The five group coordinators received training courses on data sources and electronic databases, literature search strategies, the scientific revision methods of quality assessment, and the construction of an evidence matrix. Working plan and methods The working plan identified the following step: definition of the controversial issues and identification of documents for a systematic literature review. A specific methodology to classify the selected evidence was used that required the evaluation of the quality of review documents and statement documents and evaluation of the quality of original research. An original method to assess review documents and statement documents was proposed. A matrix model to extract and evaluate the evidence from original studies was designed using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, cohorts, and retrospective studies. Quality of evidence A modified GRADE working group method was applied for grading quality of evidence and strength of recommendations. The working groups reviewed the available studies and formulated recommendations to be voted on at the national consensus conference held in Rome in June 2009.
Summary Background The treatment of severe bloodstream infections (sepsis, endocarditis, and infections of vascular prostheses) caused by Gram-positive microorganisms is made even more difficult by ...the emergence of resistant strains. The introduction of new antibiotics with activity against these strains has created new opportunities, but many controversial issues remain. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues concerned the duration of therapy and role of aminoglycosides and teicoplanin in the treatment of Gram-positive bacterial endocarditis, the optimal use of the new antibiotics in the treatment of bloodstream infections caused by resistant Gram-positive strains, and the use of microbiological techniques (i.e., bactericidal serum testing and synergy testing) and of pharmacokinetic data (e.g., monitoring of plasma levels of antibiotics) in the treatment of difficult-to-treat Gram-positive bloodstream infections. Methods A systematic literature search of randomized controlled trials and/or non-randomized studies was performed mainly using the MEDLINE database. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for non-randomized studies. The GRADE method for grading the quality of evidence and strength of recommendation was applied.
Summary Background Hospital-associated pneumonia (HAP) remains an important cause of morbidity and mortality despite advances in antimicrobial therapy. Many aspects of the treatment of HAP caused by ...multi-resistant Gram-positive microorganisms have been extensively studied, but controversial issues remain. Controversial issues The aim of this GISIG (Gruppo Italiano di Studio sulle Infezioni Gravi) working group – a panel of multidisciplinary experts – was to define recommendations for some controversial issues using an evidence-based and analytical approach. The controversial issues were: (1) Is combination antibiotic therapy or monotherapy more effective in the treatment of HAP? (2) What role do pharmacokinetic/pharmacodynamic antibiotic features have as a guide in the selection of treatment for HAP? (3) Is a de-escalation approach for the management of HAP effective? An analysis of the studies published up until April 2009 is presented and discussed in detail. Methods A systematic literature search using PubMed, MEDLINE, and EMBASE databases and the Cochrane Library was performed. A matrix was created to extract evidence from original studies using the CONSORT method to evaluate randomized clinical trials and the Newcastle–Ottawa Quality Assessment Scale for case–control studies, longitudinal cohorts, and retrospective studies. The GRADE method for grading quality of evidence was applied.
Molecular testing of 270 consecutive nasopharyngeal swab samples taken in May and June 2009 and 274 samples from patients hospitalized between July and December 2009 showed similar findings of ...respiratory viruses, with influenza A pandemic virus H1N1/09 being the most represented, followed by human parainfluenza virus type 3 and rhinoviruses. Statistical analyses suggested virus cocirculation in the absence of viral interference.
Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has ...resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.
Hairy cell leukemia (HCL) derives from a mature B cell and expresses markers associated with activation. Analysis of immunoglobulin variable region genes has revealed somatic mutation in most cases, ...consistent with an origin from a cell that has encountered the germinal center. One unusual feature of hairy cells (HCs) is the frequent expression of multiple immunoglobulin heavy chain isotypes, with dominance of immunoglobulin (Ig)–G3, but only a single light chain type. The origin and clonal relationship of these isotype variants have been unclear. In order to probe the isotype switching status of HCL, RNA transcripts of VHDJH– constant region sequences from 5 cases of typical HCL, all expressing multiple surface immunoglobulin isotypes, were analyzed. Tumor VHDJH-Cμ sequences were identified and found to be somatically mutated (range, 1.4% to 6.5%), with a low level of intraclonal heterogeneity. Additional immunoglobulin isotypes of identical VHDJHsequence were also identified, including IgD (5 of 5), IgG3 (5 of 5), IgG1 (3 of 5), IgG2 (2 of 5), IgA1 (4 of 5), and IgA2 (1 of 5). Derivation of multiple isotypes from individual cells was demonstrated by analyzing transcripts in single sorted cells from one patient, with evidence for coexistence of isotype variants in 10 of 10 cells. These findings indicate that clonally related multiple isotypes coexist in single HCs, with individual isotypes presumably generated via RNA splicing. Production of IgG3 appears common, but IgG1, IgG2, IgA1, and IgA2 also arise, indicating a continuing influence of a directed process on the tumor clone. These HCs appear to be arrested at the point of isotype switch, where RNA processing may precede deletional recombination.
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