GOALS:We describe the epidemiology of outpatients newly diagnosed with chronic alcoholic liver disease and describe predictors of cirrhosis and referral for specialty care.BACKGROUND:Alcohol is a major cause of liver disease in the United States. Most previous work has described hospitalized patients.STUDY:Participants were identified through prospective population-based surveillance in gastroenterology practices Multnomah County, Oregon and New Haven County, Connecticut; and primary care and gastroenterology practices from Kaiser Permanente Northern California in Alameda County during 1999 to 2001. Patients were interviewed, a blood specimen obtained, and their medical record reviewed.RESULTS:We identified 82 patients from gastroenterology practices with newly diagnosed alcoholic liver disease. Their median age was 50.0 years. 72.0% were male and 79.3% were White. The median age at initiation of alcohol use was 17.0 years. 43.9% of patients had evidence of cirrhosis at the time of diagnosis. Only 40.2% reported alcohol as the cause of their liver disease. Patients with cirrhosis were more likely to be older, have a higher median number of years of heavy alcohol consumption, and to have been hospitalized for a liver-related complication than noncirrhotic patients. An additional 83 primary care patients were more likely to be older, to be drinking alcohol at study interview, and to not have cirrhosis than patients referred for gastroenterology care.CONCLUSIONS:Patients with alcoholic liver disease may present at a late stage and may not identify alcohol as a cause for their liver disease. Improved patient screening and education may limit morbidity and mortality.

Obesity appears to be a risk factor for hepatic steatosis, which has been implicated in the development of hepatic fibrosis in patients with hepatitis C virus infection. We conducted the current study to examine whether obesity is associated with hepatic steatosis among patients with chronic hepatitis C identified from a population-based cohort. Study participants were persons with chronic hepatitis C who had had a liver biopsy, identified from a population-based study of persons with newly identified chronic liver disease conducted in gastroenterology practices. Data were collected through patient interviews, medical record abstraction, and review of previously performed liver biopsies. The outcome variable of interest was significant steatosis, defined as steatosis grade > or =2 determined from liver biopsy samples. Univariate and multivariate analyses were performed using logistic regression techniques. The analysis included 450 patients with chronic hepatitis C with available liver biopsy slides. Overall, only 15.8% of subjects had significant hepatic steatosis (grade > or =2), while 35.9% of obese subjects had significant steatosis. In multivariate analysis, significant fibrosis (defined as > or = grade 2) (odds ratio [OR], 3.43; 95% confidence interval [CI], 1.59-7.37), obesity (OR, 3.32; 95% CI, 1.84-5.98), genotype 3 (OR, 2.5; 95% CI, 1.09-5.75), and the presence of multiple metabolic comorbidities (OR, 1.91; 95% CI, 0.88-4.11) were independently associated with steatosis. In this unique United States cohort of patients with newly diagnosed chronic liver disease due to hepatitis C, obesity was independently associated with hepatic steatosis. The results of this study provide additional evidence that obesity worsens liver damage in patients with chronic hepatitis C, and suggest a role for weight loss as a treatment modality in these patients.

Hepatitis C (HCV) is a leading cause of chronic liver disease in the United States. Connecticut has a registry of laboratory reported cases of HCV. These reports include limited patient-level information. Using a one-page abstraction instrument, we used this registry to contact providers by fax to obtain contact, epidemiologic, and clinical information on Waterbury residents with newly reported HCV. We offered to perform the data abstraction if desired by the physician. In 2004, 376 new cases of HCV were reported. Eighty-eight percent of abstraction instruments were returned; most were completed by physician office staff. These included detailed information on age, race, gender, risk factors for acquisition of infection, clinical status, and confirmatory testing. Many patients appear to not have adequate follow-up for the management of this infection. Fax-back surveillance in the case of HCV is feasible and provides much-needed patient-level information.

ABSTRACT Background: Recognition of bioterrorism-related infections by hospital and emergency department clinicians may be the first line of defense in a bioterrorist attack. Methods: We identified unexplained infectious deaths consistent with the clinical presentation of anthrax, tularemia, smallpox, and botulism using Connecticut death certificates and hospital chart information. Minimum work-up criteria were established to assess the completeness of diagnostic testing. Results: Of 4558 unexplained infectious deaths, 133 were consistent with anthrax (2.9%) and 6 (0.13%) with tularemia. None were consistent with smallpox or botulism. No deaths had anthrax or tularemia listed in the differential diagnosis or had disease-specific serology performed. Minimum work-up criteria were met for only 53% of cases. Conclusions: Except for anthrax, few unexplained deaths in Connecticut could possibly be the result of the bioterrorism agents studied. In 47% of deaths from illnesses that could be anthrax, the diagnosis would likely have been missed. As of 2004, Connecticut physicians were not well prepared to intentionally or incidentally diagnose initial cases of anthrax or tularemia. More effective clinician education and surveillance strategies are needed to minimize the potential to miss initial cases in a bioterrorism attack. ( Disaster Med Public Health Preparedness . 2008;2:87–94)

The United States National Center for Health Statistics (NCHS) uses death certificate data to estimate the burden of serious disease. This study aimed to determine the accuracy of the NCHS method for estimating the burden of chronic liver disease (CLD).The authors identified death certificates of New Haven County residents who died from October 1999-September 2000 that were assigned one of 115 ICD-10 codes that might indicate CLD. They reviewed medical charts, medical examiner records and a certifier questionnaire to determine whether CLD was the cause of death.Using the authors' determination of CLD status as the gold standard, the specificity of the NCHS classification was high (86%), but the sensitivity was low (36%). The authors found that adding selected ICD-10 codes to those considered by the NCHS to be CLD (certain CLD malignancies and viral hepatitis) could improve sensitivity. Ensuring that deaths attributed by certifiers to "End Stage Liver Disease" were coded as CLD could also improve completeness. These modifications could increase sensitivity substantially with little effect on specificity.The NCHS method may understate the CLD burden substantially which could have a detrimental effect on planning for and evaluating prevention and treatment. Modifications could improve completeness.

OBJECTIVES:Chronic liver disease (CLD) is an important cause of morbidity and mortality, but the epidemiology is not well described. We conducted prospective population-based surveillance to estimate newly diagnosed CLD incidence, characterize etiology distribution, and determine disease stage.METHODS:We identified cases of CLD newly diagnosed during 1999-2001 among adult county residents seen in any gastroenterology practice in New Haven County, Connecticut; Multnomah County, Oregon; and Northern California Kaiser Permanente Medical Care Program (KPMCP, Oakland, California [total population 1.48 million]). We defined CLD as abnormal liver tests of at least 6 months' duration or pathologic, clinical, or radiologic evidence of CLD. Consenting patients were interviewed, a blood specimen obtained, and the medical record reviewed.RESULTS:We identified 2,353 patients with newly diagnosed CLD (63.9 cases/100,000 population), including 1,225 hepatitis C patients (33.2 cases/100,000). Men aged 45-54 yr had the highest hepatitis C incidence rate (111.3/100,000). Among 1,040 enrolled patients, the median age was 48 yr (range 19-86 yr). Hepatitis C, either alone (442 [42%]) or in combination with alcohol-related liver disease (ALD) (228 [22%]), accounted for two-thirds of the cases. Other etiologies included nonalcoholic fatty liver disease (NAFLD, 95 [9%]), ALD (82 [8%]), and hepatitis B (36 [3%]). Other identified etiologies each accounted for <3% of the cases. A total of 184 patients (18%) presented with cirrhosis, including 44% of patients with ALD.CONCLUSIONS:Extrapolating from this population-based surveillance network to the adult U.S. population, approximately 150,000 patients with CLD were diagnosed in gastroenterology practices each year during 1999-2001. Most patients had hepatitis C; heavy alcohol consumption among these patients was common. Almost 20% of patients, an estimated 30,000 per year, had cirrhosis at presentation. These results provide population-level baseline data to evaluate trends in identification of patients with CLD in gastroenterology practices.

Background & Aims: Assessment of liver histology has an important role in the management of chronic liver disease. It is not clear whether there are interobserver variabilities between hepatopathologists and general community pathologists. We evaluated the effect of type of pathologist and biopsy specimen size on interobserver agreement for hepatic fibrosis. Methods: Subjects were identified from a population-based sample of adults from a chronic liver disease surveillance network. Biopsy slides from 391 hepatitis C patients who had undergone liver biopsy were obtained and read by 2 study hepatopathologists blinded to the patients' diagnoses (the gold standard). The interobserver agreement of the fibrosis stage between the hepatopathologists and the general pathologists' report were evaluated by kappa index. Results: There was complete agreement between the study pathologist and community pathologist in 49.9% of biopsy specimens. The overall kappa index across all stages of fibrosis was 0.409, with the best agreement occurring at higher stages of fibrosis (kappa: 0.482 for stage 3, 0.776 for stage 4). Overall agreement was good (kappa, 0.465) when biopsy samples were greater than 1.5 cm in size. The community pathologist understaged fibrosis in 73% of biopsy specimens with disagreement. A total of 26% of patients with stages 2 to 4 fibrosis were understaged by the community pathologist. Conclusions: Results from this population-based study show good overall interobserver agreement between hepatopathologists and general pathologists when determining fibrosis stage in liver biopsy specimens from hepatitis C patients when liver biopsy sizes are adequate. However, community pathologists tended to understage fibrosis, which could keep patients from receiving proper treatment.

Chronic viral hepatitis can cause cirrhosis. Viral hepatitis-related cirrhosis may be causing an increasing health burden since exposure to hepatitis B virus and hepatitis C virus in the United States increased starting in the 1960s. Using hospital discharge data, we estimated the number of adult New Haven County residents hospitalized for cirrhosis and examined the proportion caused by chronic viral hepatitis. Data on etiology were obtained from hospital discharge records, death certificate information, and New Haven County Liver Study records. From 1 October 1999 to 30 September 2000, 269 adult New Haven County residents were hospitalized for cirrhosis in a New Haven County hospital, for an incidence of 43.2 per 100,000 population. The burden of viral hepatitis-related cirrhosis was 15.9 per 100,000. Hepatitis C virus was the most common viral etiology. Given the long period between initial infection and clinical decompensation, screening and treatment programs aimed at reducing viral hepatitis-related morbidity should reduce hospitalization rates.

The purpose of this study is to examine the association of alcohol abuse and injection drug use (IDU) with the immunologic and virologic responses to highly active antiretroviral treatment (HAART) in urban community health clinics. The medical records of 293 HIV-infected adult patients who visited either of two urban health clinics in New Haven, Connecticut, from June 2003 to December 2004 were retrospectively reviewed. Changes in mean CD4 lymphocyte counts and undetectable viral loads were compared before and after the initiation of HAART for patients categorized into one of four substance abuse groups: history of neither alcohol abuse nor IDU, alcohol abuse only, IDU only, or both. Unadjusted mean improvements in CD4 count for the four groups were 136, 97, 20, and 27, respectively. In a linear regression model adjusted for age, gender, and baseline CD4 count, history of IDU only (P = 0.037) and a combination of alcohol abuse and IDU (P = 0.038) were associated with a lesser increase in CD4 count after HAART compared with those with neither alcohol nor IDU. No significant associations were found between substance abuse history and changes in detectable viral load. Our results show that many patients at urban health clinics have a history of either injection drug use or alcohol abuse, and that injection drug use is negatively associated with the immunologic response to HAART in urban HIV-infected individuals. This study highlights the importance for clinicians of understanding the negative associations of substance abuse with the treatment response of HIV-infected patients at urban health centers.

Background: Nosocomial bloodstream infections are associated with increased hospital costs in adult and pediatric patients. Candida is an increasingly important nosocomial pathogen within intensive care nurseries. The purpose of this study was to determine the attributable cost of candidemia in neonates. Methods: This case-control study included all neonates with candidemia receiving care in hospitals in Connecticut and in Baltimore County and the city of Baltimore, MD. We identified 47 cases and 130 control patients. Multivariable linear regression was used to control for state, birth weight and mortality to determine the effect of candidemia on length of stay, cost per day and total hospital costs. Results: Candidemia was associated with a $28,000 increase in total hospital costs in multivariable analysis. This increase in total cost was the result of both an increase in costs per day and length of hospital stay. Other cost-increasing variables included in the analysis were: state of origin (Connecticut), survival and decreasing birth weight. Conclusions: This represents the first study of the adjusted costs of candidemia in neonates. In addition to high mortality, candidemia was associated with increased hospital costs. This cost analysis could be helpful in determining the financial benefits of preventing candidemia in high risk neonates.

ABSTRACT d -Arabinitol (DA) is a useful diagnostic marker for candidiasis in patients with neutropenia and other high-risk groups, but its use in unselected patients with a broad range of underlying diseases and conditions has not been studied. We used an automated enzymatic fluorometric assay to measure serum DA/creatinine ratios (DA/cr's) in 30 healthy adults, 100 hospitalized controls without Candida fungemia, and 83 patients from a study of all Candida fungemias in Connecticut between October 1998 and September 1999. Sixty-three of 83 (76%) fungemic patients and 11 of 100 (11%) nonfungemic controls had serum DA/cr's ≥3.9 μM/mg/dl (mean + 3 standard deviations for 30 healthy adults). High serum DA/cr's were less frequent in patients with cancer or fungemia caused by the DA nonproducer Candida glabrata than in patients with cancer or fungemia caused by a DA producer, C. albicans , C. tropicalis , or C. parapsilosis . The serum DA/cr was first ≥3.9 μM/mg/dl before, on the same day as, or after the first positive blood culture was drawn for 30 (36%), 22 (27%), and 11 (13%) fungemia patients, respectively. Mortality did not differ significantly among the patients with high or normal initial or peak serum DA/cr's, but mortality was higher if any serum DA/cr value was ≥3.9 μM/mg/dl 3 or more days after the onset of fungemia (18/27 versus 4/24 patients, respectively; P < 0.001). We conclude that serum DA/cr's are useful both for the initial diagnosis of Candida fungemia and for prognostic purposes for unselected patients with a broad range of underlying diseases and conditions.

ABSTRACT One hundred seven Candida bloodstream isolates (51 C. albicans , 24 C. glabrata , 13 C. parapsilosis , 13 C. tropicalis , 2 C. dubliniensis , 2 C. krusei , and 2 C. lusitaniae strains) from patients treated with amphotericin B alone underwent in vitro susceptibility testing against amphotericin B using five different methods. Fifty-four isolates were from patients who failed treatment, defined as death 7 to 14 days after the incident candidemia episode, having persistent fever of ≥5 days' duration after the date of the incident candidemia, or the recurrence of fever after two consecutive afebrile days while on antifungal treatment. MICs were determined by using the Clinical Laboratory Standards Institute (formally National Committee for Clinical Laboratory Standards) broth microdilution procedure with two media and by using Etest. Minimum fungicidal concentrations (MFCs) were also measured in two media. Broth microdilution tests with RPMI 1640 medium generated a restricted range of MICs (0.125 to 1 μg/ml); the corresponding MFC values ranged from 0.5 to 4 μg/ml. Broth microdilution tests with antibiotic medium 3 produced a broader distribution of MIC and MFC results (0.015 to 0.25 μg/ml and 0.06 to 2 μg/ml, respectively). Etest produced the widest distribution of MICs (0.094 to 2 μg/ml). However, none of the test formats studied generated results that significantly correlated with therapeutic success or failure.

BACKGROUND:Almost one-third of patients with bloodstream infections with Candida species (candidemia) have onset of disease that occurs outside of the hospital or < or = 2 days after hospital admission (i.e., community-onset candidemia). We compared the characteristics of patients who developed candidemia by the timing of onset of infection.METHODS:Incident episodes of candidemia were identified through active, population-based surveillance in Connecticut and in Baltimore and Baltimore County, Maryland, during 1 October 1998-30 September 2000. The molecular subtypes of a sample of 45 Candida parapsilosis isolates were evaluated using Southern blots hybridized with the complex probe Cp3-13.RESULTS:Overall, 356 (31%) of the 1143 incident episodes of candidemia were classified as community-onset disease (occurring < or = 2 days after hospital admission), and 132 (37%) were caused by Candida albicans, 89 (25%) were caused by Candida glabrata, 57 (16%) were caused by C. parapsilosis, and 53 (15%) were caused by Candida tropicalis. Community-onset disease was less likely to be associated with concurrent immunosuppressive therapy, recent surgery, or use of a central venous catheter, compared with inpatient disease. Among patients with community-onset disease, the median time from blood culture to initiation of antifungal treatment was 2.7 days, the 30-day case-fatality rate was 26%, and 262 patients (75%) had been hospitalized at least once in the previous 3 months. Although there were few differences between patients with very recent hospitalization (in the previous 1 month), less recent hospitalization (previous 1-3 months), and no documented past hospitalization, C. parapsilosis was more frequently associated with community-onset disease as hospitalization became more distant. C. parapsilosis strains tended to be unique to the patient, with little similarity found between strain types, on the basis of epidemiologic classification of patients.CONCLUSION:We report that community-onset candidemia is common and occurs in patients with extensive contact with the health care system. Disease caused by C. parapsilosis tends to involve unique strains.

OBJECTIVE: To determine the mortality, hospital stay, and total hospital charges and cost of hospitalization attributable to candidemia by comparing patients with candidemia with control-patients who have otherwise similar illnesses. Prior studies lack broad patient and hospital representation or cost-related information that accurately reflects current medical practices.DESIGN: Our case-control study included case-patients with candidemia and their cost-related data, ascertained from laboratory-based candidemia surveillance conducted among all residents of Connecticut and Baltimore and Baltimore County, Maryland, during 1998 to 2000. Control-patients were matched on age, hospital type, admission year, discharge diagnoses, and duration of hospitalization prior to candidemia onset.RESULTS: We identified 214 and 529 sets of matched case-patients and control-patients from the two locations, respectively. Mortality attributable to candidemia ranged between 19% and 24%. On multivariable analysis, candidemia was associated with mortality (OR, 5.3 for Connecticut and 8.5 for Baltimore and Baltimore County; P < .05), whereas receiving adequate treatment was protective (OR, 0.5 and 0.4 for the two locations, respectively; P < .05). Candidemia itself did not increase the total hospital charges and cost of hospitalization; when treatment status was accounted for, having received adequate treatment for candidemia significantly increased the total hospital charges and cost of hospitalization ($6,000 to $29,000 and $3,000 to $22,000, respectively) and the length of stay (3 to 13 days).CONCLUSION: Our findings underscore the burden of candidemia, particularly regarding the risk of death, length of hospitalization, and cost associated with treatment.

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.