Pre- and intraoperative variables affecting early outcomes in elderly patients undergoing pancreaticoduodenectomy

AbstractBackgroundConflicting data exist regarding the safety of pancreatic resections in elderly patients. In this study we compared early complication and mortality rates between patients younger and older than 80 years of age who underwent pancreaticoduodenectomy using a validated national database.MethodsThe National Surgical Quality Improvement Program (NSQIP) database for 2005–2009 was used for this retrospective analysis. The primary outcome measures for our analysis were 30-day postoperative mortality, major complication rate and overall complication rate.ResultsA total of 6293 patients who underwent PD for any cause were included in the analysis. Of these, 9.4% were aged ≥80 years. The incidence of 30-day mortality was significantly higher in patients aged ≥80 years (6.3%) than in those aged <80 years (2.7%). Older patients were also noted to have higher rates of overall complications and serious complications. On multivariate analysis, age, ASA (American Society of Anesthesiologists) classification, reduced functional status, history of dyspnoea, and need for intraoperative transfusion were risk factors associated with the occurrence of overall complications, serious complications and postoperative mortality.ConclusionsThis study shows that age among other factors is a determinant of postoperative morbidity and mortality following PD

Forum Report: Issues in the Evaluation of Diagnostic Tests, Use of Historical Controls, and Merits of the Current Multicenter Collaborative Groups

This forum report contains conclusions about 3 different issues relevant to conducting clinical trials in deep mycoses. (1) Trials of diagnostic tests for deep mycoses must define the population appropriate for testing and the clinical question being asked. The unanswered question for the serum Aspergillus galactomannan assay is whether knowledge of results can change use of empirical therapy to treat febrile patients at high risk of invasive aspergillosis. (2) Use of historical controls is suboptimal but offers a pragmatic solution for studying rare mycoses; use of contemporaneous controls, matched for critical variables and evaluated by a blinded data review committee using detailed criteria, appears optimal. (3) Established groups of independent investigators, such as the European Organization for Research on Treatment of Cancer's Invasive Fungal Infections Group and National Institute of Allergy and Infectious Diseases's Bacteriology and Mycology Study Group, provide a pool of experienced investigators, defined operating rules, impartiality, and specialized expertise. Considering the enormous investment required for adequately powered efficacy trials of antifungal agents and the importance of these trials to guide clinical practice, use of collaborative groups outweighs the extra administrative time that is sometimes require

Forum Report: Issues in the Design of Trials of Drugs for the Treatment of Invasive Aspergillosis

A recent trial of drugs for invasive aspergillosis was used as a background for discussing critical features in the design of antifungal trials. The study under discussion allowed stopping either drug without classifying the patient as having treatment failure, so the trial should be understood as a comparison of 2 treatment strategies, not just 2 drugs. Although the study was a noninferiority trial, the outcome permitted a claim of superiority. Use of the category of "probable” in addition to "proven” aspergillosis permitted inclusion of patients for whom the diagnosis was less certain but who were still early enough in the disease progression to respond to therapy. Different opinions still exist about some of the criteria for the diagnosis of "probable” aspergillosis. A blinded data review committee was helpful in evaluating efficacy in this unblinded trial but had limited value in assessing toxicity. An understanding of these features of design of antifungal drug trials is important in applying the results to clinical practic

Forum Report: Issues in Clinical Trials of Empirical Antifungal Therapy in Treating Febrile Neutropenic Patients

There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of feve

Mortality After Clinical Management of Aids-Associated Cryptococcal Meningitis in Kenya

Background: Cryptococcal meningitis (CM) is an increasingly prevalent  infection among HIV/AIDS patients and is becoming a leading cause of  morbidity and mortality in Africa. The short-term prognosis and  management of patients with CM may be improved by identifying factors leading to mortality in patients with CM.Objective: To assess the clinical management and mortality associated with cryptococcal meningitis (CM) in patients with acquired  immunodeficiency syndrome (AIDS) in Kenya.Design: A retrospective study.Setting: Kenyatta National Hospital and Mbagathi District Hospital, between August 2008 and March 2009.Subjects: Seventy six HIV-infected patients confirmed to be CM positive.Results: Results show that 30 (40%) of 76 patients diagnosed with CM died during hospitalisation after a median hospital stay of ten days (range, 2-73 days). Significant predictors of mortality in the univariate model were Mycobacterium tuberculosis (TB) co-infection (P = 0.04), having been diagnosed with a co-morbid condition such as diabetes mellitus, oral candidiasis and hypertension (P = 0.01), and a low median CD4+ T lymphocyte count (P &lt; 0.001). The multivariable model revealed that male sex, previous or current anti-retroviral therapy (ART) at admission and CD4+ T lymphocyte count less than 50 were significant predictors of mortality. Conversely, a minimum of two weeks of amphotericin B treatment (P &lt; 0.001), initiation of ART (P = 0.007) and monitoring of creatinine and electrolyte levels (P = 0.02) were significantly associatedwith survival in the univariate model.Conclusions: CM-associated mortality in Kenya is high; there is an  opportunity to improve the management and the short-term outcomes of hospitalised HIV positive patients with CM in Kenya

Real-world comparison of two molecular methods for detection of respiratory viruses

Background: Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories.Methods: We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) and individual real-time RT-PCR (RT-rtPCR).Results: Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV) and respiratory syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection.Conclusions: Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy

Clinical Practice Guidelines for the Management Candidiasis: 2009 Update by the Infectious Diseases Society of America

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised documen

Description of Cryptococcosis Following SARS-CoV-2 Infection: A Disease Survey Through the Mycosis Study Group Education and Research Consortium (MSG-19)

BACKGROUND: Invasive fungal infections have been described throughout the COVID-19 pandemic. Cryptococcal disease after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in several isolated case reports and 1 larger case series. We sought to describe cryptococcal infections following SARS-CoV-2 through establishing a database to investigate underlying risk factors, disease manifestations, and outcomes. METHODS: We created a crowdsourced call for cases solicited through the Mycoses Study Group Education and Research Consortium, the Centers for Disease Control and Prevention Emerging Infectious Diseases Network, and infectious diseases Twitter groups. Data were collected in a web-based and secure REDCap survey without personal identifiers. RESULTS: Sixty-nine cases were identified and submitted by 29 separate institutional sites. Cryptococcosis was diagnosed a median of 22 days (interquartile range, 9-42 days) after SARS-CoV-2 infection. Mortality among those with available follow-up was 72% (26/36) for the immunocompetent group and 48% (15/31) for the immunocompromised group (likelihood ratio, 4.01; P = .045). We observed a correlation between disease manifestation (central nervous system infection, proven/probable disseminated disease, and respiratory) and mortality (P = .002). CONCLUSIONS: The mortality rate of 59% for patients with cryptococcosis following SARS-CoV-2 is higher than that of modern Cryptococcus cohorts. There was an association between immunocompromised status and cryptococcal disease manifestations as well as mortality. Moreover, our series emphasizes the need for clinical and laboratory assessment of opportunistic infections beyond 30 days when concerning symptoms develop