Maureen Phelan

Trends in Mortality Due to Invasive Mycotic Diseases in the United States, 1980–1997

To determine national trends in mortality due to invasive mycoses, we analyzed National Center for Health Statistics multiple-cause-of-death record tapes for the years 1980 through 1997, with use of their specific codes in the International Classification of Diseases, Ninth Revision (ICD-9 codes 112.4-118 and 136.3). In the United States, of deaths in which an infectious disease was the underlying cause, those due to mycoses increased from the tenth most common in 1980 to the seventh most common in 1997. From 1980 through 1997, the annual number of deaths in which an invasive mycosis was listed on the death certificate (multiple-cause [MC] mortality) increased from 1557 to 6534. In addition, rates of MC mortality for the different mycoses varied markedly according to human immunodeficiency virus (HIV) status but were consistently higher among males, blacks, and persons > or =65 years of age. These data highlight the public health importance of mycotic diseases and emphasize the need for continuing surveillance.

Incidence of Bloodstream Infections Due to Candida Species and In Vitro Susceptibilities of Isolates Collected from 1998 to 2000 in a Population-Based Active Surveillance Program

ABSTRACT To determine the incidence of Candida bloodstream infections (BSI) and antifungal drug resistance, population-based active laboratory surveillance was conducted from October 1998 through September 2000 in two areas of the United States (Baltimore, Md., and the state of Connecticut; combined population, 4.7 million). A total of 1,143 cases were detected, for an average adjusted annual incidence of 10 per 100,000 population or 1.5 per 10,000 hospital days. In 28% of patients, Candida BSI developed prior to or on the day of admission; only 36% of patients were in an intensive care unit at the time of diagnosis. No fewer than 78% of patients had a central catheter in place at the time of diagnosis, and 50% had undergone surgery within the previous 3 months. Candida albicans comprised 45% of the isolates, followed by C. glabrata (24%), C. parapsilosis (13%), and C. tropicalis (12%). Only 1.2% of C. albicans isolates were resistant to fluconazole (MIC, ≥64 μg/ml), compared to 7% of C. glabrata isolates and 6% of C. tropicalis isolates. Only 0.9% of C. albicans isolates were resistant to itraconazole (MIC, ≥1 μg/ml), compared to 19.5% of C. glabrata isolates and 6% of C. tropicalis isolates. Only 4.3% of C. albicans isolates were resistant to flucytosine (MIC, ≥32 μg/ml), compared to <1% of C. parapsilosis and C. tropicalis isolates and no C. glabrata isolates. As determined by E-test, the MICs of amphotericin B were ≥0.38 μg/ml for 10% of Candida isolates, ≥1 μg/ml for 1.7% of isolates, and ≥2 μg/ml for 0.4% of isolates. Our findings highlight changes in the epidemiology of Candida BSI in the 1990s and provide a basis upon which to conduct further studies of selected high-risk subpopulations.

The Changing Epidemiology of Cryptococcosis: An Update from Population-Based Active Surveillance in 2 Large Metropolitan Areas, 1992–2000

To examine trends in the incidence and epidemiology of cryptococcosis, active, population-based surveillance was conducted during 1992-2000 in 2 areas of the United States (the Atlanta, Georgia, and Houston, Texas, metropolitan areas; combined population, 7.4 million). A total of 1491 incident cases were detected, of which 1322 (89%) occurred in HIV-infected persons. The annual incidence of cryptococcosis per 1000 persons with AIDS decreased significantly during the study period, from 66 in 1992 to 7 in 2000 in the Atlanta area, and from 24 in 1993 to 2 in 1994 in the Houston area. Poisson regression analysis revealed that African American persons with AIDS were more likely than white persons with AIDS to develop disease. Less than one-third of all HIV-infected persons with cryptococcosis were receiving antiretroviral therapy before diagnosis. Our findings suggest that HIV-infected persons who continue to develop cryptococcosis in the era of highly active antiretroviral therapy (HAART) in the United States are those with limited access to health care. More efforts are needed to expand the availability of HAART and routine HIV care services to these persons.

Risk factors for morbidity and mortality after colectomy for colon cancer

PURPOSE: Comorbid conditions affect the risk of adverse outcomes after surgery, but the magnitude of risk has not previously been quantified using multivariate statistical methods and prospectively collected data. Identifying factors that predict results of surgical procedures would be valuable in assessing the quality of surgical care. This study was performed to define risk factors that predict adverse events after colectomy for cancer in Department of Veterans Affairs Medical Centers. METHODS: The National Veterans Affairs Surgical Quality Improvement Program contains prospectively collected and extensively validated data on more than 415,000 surgical operations. All patients undergoing colectomy for colon cancer from 1991 to 1995 who were registered in the National Veterans Affairs Surgical Quality Improvement Program database were selected for study. Independent variables examined included 68 preoperative and 12 intraoperative clinical risk factors; dependent variables were 21 specific adverse outcomes. Stepwise logistic regression analysis was used to construct models predicting the 30-day mortality rate and 30-day morbidity rates for each of the ten most frequent complications. RESULTS: A total of 5,853 patients were identified; 4,711 (80 percent) underwent resection and primary anastomosis. One or more complications were observed in 1,639 of 5,853 (28 percent) patients. Prolonged ileus (439/5,853; 7.5 percent), pneumonia (364/5,853; 6.2 percent), failure to wean from the ventilator (334/5,853; 5.7 percent), and urinary tract infection (292/5,853; 5 percent) were the most frequent complications. The 30-day mortality rate was 5.7 percent (335/5,853). For most complications, 30-day in-hospital mortality rates were significantly higher for patients with a complication than for those without. Thirty-day mortality rates exceeded 50 percent if postoperative coma, cardiac arrest, a pre-existing vascular graft prosthesis that failed after colectomy, renal failure, pulmonary embolism, or progressive renal insufficiency occurred. Preoperative factors that predicted a high risk of 30-day mortality included ascites, serum sodium >145 mg/dl, “do not resuscitate” status before surgery, American Society of Anesthesiologists classes III and IV OR V, and low serum albumin. CONCLUSIONS: Mortality rates after colectomy in Veterans Affairs hospitals are comparable with those reported in other large studies. Ascites, hypernatremia, do not resuscitate status before surgery, and American Society of Anesthesiologists classes III and IV OR V were strongly predictive of perioperative death. Clinical trials to decrease the complication rate after colectomy for colon cancer should focus on these risk factors.

Identifying Patient preoperative risk factors and postoperative adverse events in administrative databases: Results from the Department of Veterans Affairs National Surgical Quality Improvement program

BACKGROUND The Department of Veterans Affairs (DVA) National Surgical Quality Improvement Program (NSQIP) employs trained nurse data collectors to prospectively gather preoperative patient characteristics and 30-day postoperative outcomes for most major operations in 123 DVA hospitals to provide risk-adjusted outcomes to centers as quality indicators. It has been suggested that routine hospital discharge abstracts contain the same information and would provide accurate and complete data at much lower cost. STUDY DESIGN With preoperative risks and 30-day outcomes recorded by trained data collectors as criteria standards, ICD-9-CM hospital discharge diagnosis codes in the Patient Treatment File (PTF) were tested for sensitivity and positive predictive value. ICD-9-CM codes for 61 preoperative patient characteristics and 21 postoperative adverse events were identified. RESULTS Moderately good ICD-9-CM matches of descriptions were found for 37 NSQIP preoperative patient characteristics (61%); good data were available from other automated sources for another 15 (25%). ICD-9-CM coding was available for only 13 (45%) of the top 29 predictor variables. In only three (23%) was sensitivity and in only four (31%) was positive predictive value greater than 0.500. There were ICD-9-CM matches for all 21 NSQIP postoperative adverse events; multiple matches were appropriate for most. Postoperative occurrence was implied in only 41%; same breadth of clinical description in only 23%. In only four (7%) was sensitivity and only two (4%) was positive predictive value greater than 0.500. CONCLUSION Sensitivity and positive predictive value of administrative data in comparison to NSQIP data were poor. We cannot recommend substitution of administrative data for NSQIP data methods.

Evaluation of Four Commercially Available Rapid Serologic Tests for Diagnosis of Leptospirosis

ABSTRACT Four rapid tests for the serologic diagnosis of leptospirosis were evaluated, and the performance of each was compared with that of the current standard, the microscopic agglutination test (MAT). The four rapid tests were a microplate immunoglobulin M (IgM)-enzyme-linked immunosorbent assay (ELISA), an indirect hemagglutination assay (IHA), an IgM dipstick assay (LDS), and an IgM dot-ELISA dipstick test (DST). A panel of 276 sera from 133 cases of leptospirosis from four different geographic locations was tested as well as 642 sera from normal individuals or individuals with other infectious or autoimmune diseases. Acute-phase sera from cases (n = 148) were collected ≤14 days (median = 6.0) after the onset of symptoms, and convalescent-phase sera (n = 128) were collected ≥15 days after onset (median = 29.1). By a traditional method (two-by-two contingency table), the sensitivities for detection of leptospirosis cases were 93.2% by LDS, 92.5% by DST, 86.5% by ELISA, and 79.0% by IHA. Specificity was 98.8% by DST, 97% by ELISA and MAT, 95.8% by IHA, and 89.6% by LDS. With a latent class analysis (LCA) model that included all the rapid tests and the clinical case definition, sensitivity was 95.5% by DST, 94.5% by LDS, 89.9% by ELISA, and 81.1% by IHA. The sensitivity and specificity estimated by the traditional methods were quite close to the LCA estimates. However, LCA allowed estimation of the sensitivity of the MAT (98.2%), which traditional methods do not allow. For acute-phase sera, sensitivity was 52.7% by LDS, 50.0% by DST, 48.7% by MAT and ELISA, and 38.5% by IHA. The sensitivity for convalescent-phase sera was 93.8% by MAT, 84.4% by DST, 83.6% by LDS, 75.0% by ELISA, and 67.2% by IHA. A good overall correlation with the MAT was obtained for each of the assays, with the highest concordance being with the DST (kappa value, 0.85; 95% confidence interval [CI], 0.8 to 0.90). The best correlation was between ELISA and DST (kappa value, 0.86; 95% CI, 0.81 to 0.91). False-positive LDS results were frequent (≥20%) in sera from individuals with Epstein-Barr virus, human immunodeficiency virus, and periodontal disease and from healthy volunteers. The ease of use and significantly high sensitivity and specificity of DST and ELISA make these good choices for diagnostic testing.

Use of Real-Time PCR To Resolve Slide Agglutination Discrepancies in Serogroup Identification of Neisseria meningitidis

ABSTRACT Neisseria meningitidis is a leading cause of bacterial meningitis and septicemia in children and young adults in the United States. Rapid and reliable identification of N. meningitidis serogroups is crucial for judicious and expedient response to cases of meningococcal disease, including decisions about vaccination campaigns. From 1997 to 2002, 1,298 N. meningitidis isolates, collected in the United States through the Active Bacterial Core surveillance (ABCs), were tested by slide agglutination serogrouping (SASG) at both the ABCs sites and the Centers for Disease Control and Prevention (CDC). For over 95% of isolates, SASG results were concordant, while discrepant results were reported for 58 isolates. To resolve these discrepancies, we repeated the SASG in a blinded fashion and employed ctrA and six serogroup-specific PCR assays (SGS-PCR) to determine the genetic capsule type. Seventy-eight percent of discrepancies were resolved, since results of the SGS-PCR and SASG blinded study agreed with each other and confirmed the SASG result at either state health laboratories or CDC. This study demonstrated the ability of SGS-PCR to efficiently resolve SASG discrepancies and identified the main cause of the discrepancies as overreporting of these isolates as nongroupable. It also reemphasized the importance of adherence to quality assurance procedures when performing SASG and prompted prospective monitoring for SASG discrepancies involving isolates collected through ABCs in the United States.

Effect of infant immunisation on childhood mortality in rural Bangladesh: analysis of health and demographic surveillance data

BACKGROUND In developing countries, immunisation programmes must compete with other strategies to improve public health and quality of life. Studies of long-term effects of immunisation programmes are rare. We assessed associations between vaccinations and mortality over 15 years after the introduction of routine infant immunisation programmes in Matlab, Bangladesh. METHODS We analysed data recorded in a comprehensive health and demographic surveillance system from 1986 to 2001. We did univariate analyses and assessed vaccinations as independent factors with other variables in Cox models with time dependent covariates. FINDINGS Diphtheria-tetanus-pertussis (DTP) and oral polio vaccination were independently associated with decreased risk of death before age 9 months, as were amount of maternal education, maternal age, and birth order of the child. DTP vaccination was associated with increased survival (hazard ratio=0.76, 95% CI 0.67-0.88; p=0.001) in a model evaluating mortality between 6 weeks and 9 months of age. Measles vaccination was also associated with increased survival when data after late immunisation with DTP and Bacille Calmette-Guérin (BCG) were excluded. BCG vaccination was associated with reduced survival; however, children vaccinated with BCG during the first 6 months of life had significantly lower risk of death than those vaccinated later (hazard ratio=0.59; 95% CI 0.47-0.73; p=0.0001). INTERPRETATION By contrast with previous findings, we noted substantially reduced mortality among children who received DTP vaccine. This effect could be due to actual protection against pertussis disease and secondary illnesses or to a non-specific benefit, although we cannot rule out epidemiological artifact. Our findings show the value of population-based health surveillance systems.

Automatic Electronic Laboratory-Based Reporting of Notifiable Infectious Diseases

Electronic laboratory-based reporting, developed by the University of Pittsburgh Medical Center (UPMC) Health System, was evaluated to determine if it could be integrated into the conventional paper-based reporting system. We reviewed reports of 10 infectious diseases from 8 UPMC hospitals that reported to the Allegheny County Health Department in southwestern Pennsylvania during January 1–November 26, 2000. Electronic reports were received a median of 4 days earlier than conventional reports. The completeness of reporting was 74% (95% confidence interval [CI] 66% to 81%) for the electronic laboratory-based reporting and 65% (95% CI 57% to 73%) for the conventional paper-based reporting system (p>0.05). Most reports (88%) missed by electronic laboratory-based reporting were caused by using free text. Automatic reporting was more rapid and as complete as conventional reporting. Using standardized coding and minimizing free text usage will increase the completeness of electronic laboratory-based reporting.

Outcome after proctectomy for rectal cancer in Department of Veterans Affairs Hospitals: a report from the National Surgical Quality Improvement Program.

OBJECTIVE To define risk factors that predict adverse outcomes after proctectomy for cancer in Department of Veterans Affairs Medical Centers. SUMMARY BACKGROUND DATA Accurate presurgical assessment of the risk of perioperative complications and death is important in planning surgical therapy. METHODS The National VA Surgical Quality Improvement Program contains prospectively collected and extensively validated data on >287,000 patients. All patients undergoing proctectomy for rectal cancer from 1991 to 1995 who were registered in this data base were selected for study. Independent variables examined included 68 presurgical and 12 intraoperative clinical risk factors; dependent variables were 21 specific adverse outcomes. Stepwise logistic regression analysis was used to construct models predicting 30-day morbidity rates for each of the 10 most common complications and the 30-day mortality rate. RESULTS Five hundred ninety-one patients were identified; 467 (79%) underwent abdominoperineal resection and 124 (21%) were treated with sphincter-saving procedures. Thirty percent of patients had one or more complications after proctectomy. Prolonged ileus, urinary tract infection, pneumonia, and deep wound infection were the most frequently reported complications. The 30-day mortality rate was 3.2% (19 deaths). For most complications, 30-day mortality rates were significantly higher for patients with complications than for those without. Thirty-day mortality rates for several complications exceeded 50%: cardiac arrest requiring cardiopulmonary resuscitation, deep venous thrombosis or thrombophlebitis, coma lasting >24 hours, acute renal failure, cerebrovascular accident, and pulmonary embolism. Four presurgical factors predicted a high risk of 30-day mortality in the logistic regression analysis: elevated blood urea nitrogen level, impaired sensorium, low serum albumin concentration, and partial thromboplastin time < or =25 seconds. CONCLUSIONS Mortality rates after proctectomy in VA hospitals are comparable to those reported in other large series. Most postsurgical complications are associated with an increased 30-day mortality rate. Elevated presurgical blood urea nitrogen level, impaired sensorium, low serum albumin concentration, and partial thromboplastin time < or =25 seconds predict a high risk of 30-day mortality.