Virulence patterns of Staphylococcus aureus strains from nasopharyngeal colonization.

BACKGROUND: The prevalence of nasopharyngeal colonization with Staphylococcus aureus can reach 20-30% among the population, which can lead to invasive infection. AIM: To investigate the prevalence of colonization among different age groups, and analyse S. aureus strain-specific virulence patterns. METHOD: For analysis of the prevalence of colonization, groups consisting of newborns, healthy volunteers aged 5-60 years, and nursing home residents aged >80 years were examined with nasopharyngeal swabs. After S. aureus was cultured, genetic analysis and phenotypic virulence testing were performed by cell-based assays. FINDINGS: Among 924 volunteers, the overall colonization rate was approximately 30%, with a peak in subjects aged 5-10 years (49%). Neonates and subjects aged >80 years showed different distributions of clonal clusters. Overall, the strains of all age groups exhibited virulence characteristics that can contribute to the development of infection. In particular, the neonatal strains exhibited a high incidence of toxin genes that resulted in increased cytotoxic effects compared with the other strains tested. CONCLUSIONS: Colonizing strains showed a virulence profile in all age groups, which may lead to the establishment of invasive infection. Consequently, decolonization measures could be considered for selected patients depending on the risk of infection.

Staphylococcus aureus develops increased resistance to antibiotics by forming dynamic small colony variants during chronic osteomyelitis.

OBJECTIVES: Staphylococcus aureus osteomyelitis often develops to chronicity despite antimicrobial treatments that have been found to be susceptible in in vitro tests. The complex infection strategies of S. aureus, including host cell invasion and intracellular persistence via the formation of dynamic small colony variant (SCV) phenotypes, could be responsible for therapy-refractory infection courses. METHODS: To analyse the efficacy of antibiotics in the acute and chronic stage of bone infections, we established long-term in vitro and in vivo osteomyelitis models. Antibiotics that were tested include ß-lactams, fluoroquinolones, vancomycin, linezolid, daptomycin, fosfomycin, gentamicin, rifampicin and clindamycin. RESULTS: Cell culture infection experiments revealed that all tested antibiotics reduced bacterial numbers within infected osteoblasts when treatment was started immediately, whereas some antibiotics lost their activity against intracellular persisting bacteria. Only rifampicin almost cleared infected osteoblasts in the acute and chronic stages. Furthermore, we detected that low concentrations of gentamicin, moxifloxacin and clindamycin enhanced the formation of SCVs, and these could promote chronic infections. Next, we treated a murine osteomyelitis model in the acute and chronic stages. Only rifampicin significantly reduced the bacterial load of bones in the acute phase, whereas cefuroxime and gentamicin were less effective and gentamicin strongly induced SCV formation. During chronicity none of the antimicrobial compounds tested showed a beneficial effect on bone deformation or reduced the numbers of persisting bacteria. CONCLUSIONS: In all infection models rifampicin was most effective at reducing bacterial loads. In the chronic stage, particularly in the in vivo model, many tested compounds lost activity against persisting bacteria and some antibiotics even induced SCV formation.

A psychometric analysis of the measurement level of the rating scale, time trade-off, and standard gamble.

A fundamental assumption of utility-based analyses is that patient utilities for health states can be measured on an equal-interval scale. This assumption, however, has not been widely examined. The objective of this study was to assess whether the rating scale (RS), standard gamble (SG), and time trade-off (TTO) utility elicitation methods function as equal-interval level scales. We wrote descriptions of eight prostate-cancer-related health states. In interviews with patients who had newly diagnosed, advanced prostate cancer, utilities for the health states were elicited using the RS, SG, and TTO methods. At the time of the study, 77 initial and 73 follow-up interviews had. been conducted with a consecutive sample of 77 participants. Using a Rasch model, the boundaries (Thurstone Thresholds) between four equal score sub-ranges of the raw utilities were mapped onto an equal-interval logit scale. The distance between adjacent thresholds in logit units was calculated to determine whether the raw utilities were equal-interval. None of the utility scales functioned as interval-level scales in our sample. Therefore, since interval-level estimates are assumed in utility-based analyses, doubt is raised regarding the validity of findings from previous analyses based on these scales. Our findings need to be replicated in other contexts, and the practical impact of non-interval measurement on utility-based analyses should be explored. If cost-effectiveness analyses are not found to be robust to violations of the assumption that utilities are interval, serious doubt will be cast upon findings from utility-based analyses and upon the wisdom of expending millions in research dollars on utility-based studies.

Congestive heart failure and outpatient risk of venous thromboembolism: a retrospective, case-control study.

Although CHF has been considered a risk factor for venous thromboembolism, this has not been directly studied. We hypothesized that congestive heart failure would increase the risk of venous thromboembolism in an outpatient population, and that this risk would increase as patients' ventricular function worsened. We conducted a case-control study to examine whether CHF due to left ventricular dysfunction was an independent risk factor for acute venous thromboembolism in outpatients, once established risk factors such as recent surgery and prior venous thromboembolism are taken into account. We reviewed 106 cases of DVT and 603 controls, admitted for diabetes mellitus or infection, matched for month of admission at a VA hospital. Assignment of a diagnosis of venous thromboembolism required a definitive test, as did classification as CHF. In a logistic regression model CHF was an independent predictor of venous thromboembolism. A second logistic regression model showed that the risk of venous thromboembolism increased as the ejection fraction (EF) decreased, with an EF < 20 associated with a venous thromboembolism OR of 38.3 (95% CI 9.6, 152.5). CHF is an independent risk factor for venous thromboembolism, and the risk increases markedly as the EF decreases. These results support the use of anticoagulation in selected patients with CHF.

A trial for comparing methods for eliciting treatment preferences from men with advanced prostate cancer: results from the initial visit.

OBJECTIVE: The objective of this study was to evaluate the convergent validity of 3 types of utility measures: standard gamble, time tradeoff, and rating scale. RESEARCH DESIGN: A prospective cohort of 120 men with advanced prostate cancer were first asked to rank order 8 health states, and then utility values were obtained from each participant for each of the 8 health states through 2 of the 3 techniques evaluated (standard gamble, time tradeoff and rating scale). Participants were randomly assigned to 1 of 3 possible pairs of techniques. The validity of the 3 methods, as measured by the convergence and raw score differences of the techniques, was assessed with ANOVA. The ability of the techniques to differentiate health states was determined. The inconsistencies between rankings and utility values were also measured. Proportions of illogical utility responses were assessed as the percent of times when states with more symptoms were given higher or equal utility values than states with fewer symptoms. RESULTS: There were significant differences in raw scores between techniques, but the values were correlated across health states. Utility values were often inconsistent with the rank order of health states. In addition, utility assessment did not differentiate the health states as well as the rank order. Furthermore, utility values were often illogical in that states with more symptoms received equal or higher utility values than states with fewer symptoms. CONCLUSIONS: Use of the utility techniques in cost-effectiveness analysis and decision making has been widely recommended. The results of this study raise serious questions as to the validity and usefulness of the measures.

Correlates of physical activity in a national sample of girls and boys in grades 4 through 12.

Psychological, biological, social, and physical environmental variables were examined for their association with physical activity of young people. A national sample of 1,504 parents and children in Grades 4-12 were interviewed by telephone. Twenty-two potential determinants were assessed along with an 11-item child physical activity index (alpha = .76). Hierarchical multiple regressions were conducted separately for 6 age-sex subgroups. Percentage of variance explained ranged from 18% for boys in Grades 4-6 to 59% for girls in Grades 10-12. Three variables had strong and consistent associations with the child physical activity index that generalized across subgroups: use of afternoon time for sports and physical activity, enjoyment of physical education, and family support for physical activity. These 3 variables should be targeted for change to promote physical activity in all groups of young people.

The hospital multistay rate as an indicator of quality of care.

OBJECTIVES: To evaluate the hospital multistay rate to determine if it has the attributes necessary for a performance indicator that can be applied to administrative databases. DATA SOURCES/STUDY SETTING: The fiscal year 1994 Veterans Affairs Patient Treatment File (PTF), which contains discharge data on all VA inpatients. STUDY DESIGN: Using a retrospective study design, we assessed cross-hospital variation in (a) the multistay rate and (b) the standardized multistay ratio. A hospital's multistay rate is the observed average number of hospitalizations for patients with one or more hospital stays. A hospital's standardized multistay ratio is the ratio of the geometric mean of the observed number of hospitalizations per patient to the geometric mean of the expected number of hospitalizations per patient, conditional on the types of patients admitted to that hospital. DATA COLLECTION/EXTRACTION METHODS: Discharge data were extracted for the 135,434 VA patients who had one or more admissions in one of seven disease groups. PRINCIPAL FINDINGS: We found that 17.3 percent (28,300) of the admissions in the seven disease categories were readmissions. The average number of stays per person (multistay rate) for an average of seven months of follow-up ranged from 1.15 to 1.45 across the disease categories. The maximum standardized multistay ratio ranged from 1.12 to 1.39. CONCLUSIONS: This study has shown that the hospital multistay rate offers sufficient ease of measurement, frequency, and variation to potentially serve as a performance indicator.

Assessing the performance of utility techniques in the absence of a gold standard.

BACKGROUND: Utility techniques are the most commonly used means to assess patient preferences for health outcomes. However, whether utility techniques produce valid measures of preference has been difficult to determine in the absence of a gold standard. OBJECTIVE: To introduce and demonstrate two methods that can be used to evaluate how well utility techniques measure patients' preferences. SUBJECTS AND DESIGN: Patients treated for advanced prostate cancer (n = 57) first ranked eight health states in order of preference. Four utility techniques were then used to elicit patients' utilities for each health state. MEASURES: The rating scale, standard gamble, time trade-off, and a modified version of willingness-to-pay techniques were used to elicit patients' utilities. Technique performance was assessed by computing a differentiation and inconsistency score for each technique. RESULTS: Differentiation scores indicated the rating scale permitted respondents to assign unique utility values to about 70% of the health states that should have received unique values. When the other techniques were used, about 40% or less of the health states that should have received unique utility scores actually did receive unique utility scores. Inconsistency scores, which indicate how often participants assign utility scores that contradict how they value health states, indicated that the willingness-to-pay technique produced the lowest rate of inconsistency (10%). However, this technique did not differ significantly from the rating scale or standard gamble on this dimension. CONCLUSIONS: Differentiation and inconsistency offer a means to evaluate the performance of utility techniques, thereby allowing investigators to determine the extent to which utilities they have elicited for a given decision problem are valid. In the current investigation, the differentiation and inconsistency methods indicated that all four techniques performed at sub-optimal levels, though the rating scale out-performed the standard gamble, time trade-off, and willingness-to-pay techniques.

The association of quality of care and occurrence of in-hospital, treatment-related complications.

BACKGROUND: Little data exist supporting the association of quality of care and nonfatal adverse outcomes in hospitalized patients, yet those outcomes are routinely scrutinized in quality assessment efforts. OBJECTIVE: To determine whether measurable differences in quality of care are associated with the occurrence of non-fatal, in-hospital, and treatment-related complications. DESIGN: Retrospective cohort study. SUBJECTS: A total of 2,268 patients who were discharged alive from 9 Southwestern Veterans Affairs Medical Centers with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) or diabetes mellitus. MEASURES: Retrospective chart review was performed to collect information on patient severity of illness, in-hospital complication occurrence, and process quality of care. Process quality was assessed as the adherence scores for admission work-up and for treatment during the hospital stay. Process quality represents the proportion of applicable admission or treatment criteria that were met by that patient's care providers. Once severity of illness was taken into account Cox proportional hazards regression was used to assess the independent contribution of process quality of care to complication occurrence. RESULTS: Higher admission work-up adherence scores for COPD patients and higher treatment adherence scores for COPD and diabetes patients were associated with a lower risk of complication occurrence. The adjusted risk ratios of complications for higher versus lower adherence scores (with 95% CI) were 0.64 (0.43, 0.97) and 0.52 (0.33, 0.80) for admission and treatment, respectively, in COPD patients, and 0.51 (0.31, 0.83) for treatment in diabetics. No significant association was found in CHF patients. CONCLUSION: Better admission work-up and treatment quality in COPD patients, as well as treatment quality in diabetic patients, are associated with lower risk of nonfatal treatment-related complications in the study population.

Care provided by VA mobile clinic staff during Northridge earthquake relief.

INTRODUCTION: From 25 January 1994 to 02 February 1994, staff aboard four Veterans Affairs Mobile Clinics treated Northridge earthquake victims. This study examined the types of conditions treated by Clinic staff during the disaster. METHODS: A descriptive case series using 1,123 ambulatory encounter forms was undertaken. Case-mix was assessed by classifying diagnoses into 120 possible diagnostic clusters. RESULTS: Forty-five percent of patients were infants or children and 60% were female. The primary diagnoses were characterized by acute conditions: 1) upper respiratory infection (34.6%); 2) stress reactions (11.9%); 3) otitis media (10.1%); and injuries (8%). Two-thirds of the infants and children either had an upper respiratory infection (46.4%) or otitis media (20.1%). Increasing age indicated an increased likelihood of stress and anxiety reactions. CONCLUSIONS: The results provide additional information for agencies involved in planning for and responding to disasters. Based on the types of conditions diagnosed at the VA mobile clinics (i.e., a high prevalence of acute conditions, including stress and anxiety reactions, and the large numbers of children), staff trained in primary care, mental health, and pediatrics should be considered for relief missions that begin several days after an event resulting in a disaster.

Prevalence of fetal heart rate decelerations in self-referred low-risk patients in the third trimester.

We tested the hypotheses that fetal heart rate decelerations are present during the third trimester in most low risk pregnant women, the prevalence of decelerations is a function of the length of time fetal heart rate monitoring occurs and their presence is not associated with an adverse prognosis. We performed a retrospective chart review of 114 self-referred low-risk pregnant patients who presented to the labor and delivery triage area of a tertiary care hospital at 26-41 weeks gestation. None required admission to the hospital. The control group consisted of patients who delivered immediately before and after the delivery of the study patient. Normal long-term variability and fetal baseline heart rate were found in all electronic fetal monitoring tracings. Accelerations were present in 91% and decelerations in 65% of patients. There was no correlation between length of time of monitoring and the incidence of decelerations. At delivery, there were no differences in birthweight, gestational age, 5-min Apgar scores or cord pH between the control and study patients. Variable decelerations were a common finding in the third trimester of low-risk pregnant patients who self referred to labor and delivery triage. They were not prognostic of an adverse perinatal outcome.

International Classification of Diseases, 9th Revision, Clinical Modification codes in discharge abstracts are poor measures of complication occurrence in medical inpatients.

OBJECTIVES: The authors tested the ability of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes in discharge abstracts to identify medical inpatients who experienced an in-hospital complication, using complications identified through chart review as the gold standard. METHODS: Two sets of ICD-9-CM codes were used: an inclusive set including many medical diagnoses that may also be coexistent complicating conditions on admission rather than complications and an exclusive set consisting primarily of ICD-9-CM-specified complication and adverse drug event codes. RESULTS: Neither set performed well as a diagnostic test for complication occurrence according to receiver operating characteristic analysis (ROC areas were 0.61 for the inclusive set and 0.55 for the exclusive set). Sensitivities of the ICD-9-CM codes for complications were 0.34 for the inclusive set and 0.14 for the exclusive set. Corresponding positive predictive values were 0.32 and 0.37, respectively. Sensitivities of code definitions for individual complications were generally poor, less than 0.5 in most cases. CONCLUSIONS: The authors conclude that ICD-9-CM codes in discharge abstracts are poor measures of complication occurrence.

Acute myocardial infarction: clinical characteristics, management and outcome in a metropolitan Veterans Affairs Medical Center teaching hospital.

OBJECTIVES: The influence of race and age on thrombolytic therapy, invasive cardiac procedures and outcomes was assessed in a Veterans Affairs teaching hospital. The influence of Q wave evolution on the use of invasive cardiac procedures and outcome was also assessed. BACKGROUND: It is not well known how early revascularization procedures for acute myocardial infarction are delivered or influence survival in a Veterans Affairs patient population. METHODS: From October 1993 to October 1995, all patients with myocardial infarction were identified by elevated creatine kinase, MB fraction (CK-MB) and one of the following: chest pain or shortness of breath during the preceding 24 h or electrocardiographic (ECG) abnormalities. RESULTS: Racial groups were similar in terms of age, time to ECG, peak CK and length of hospital stay. Mortality increased with age (odds ratio [OR] 1.93, 95% confidence interval [CI] 1.33 to 2.81). A trend toward increased mortality occurred for race other than Caucasian. Patients meeting ECG criteria were given thrombolytic agents in 49% of cases, but age, comorbidity count and Hispanic race decreased the probability of thrombolytic use. Cardiac catheterization was performed more often after thrombolytic agents (OR 1.85, 95% CI 0.97 to 3.54), but less often in African-Americans (OR 0.59, 95% CI 0.35 to 1.02), older patients (OR 0.39, 95% CI 0.24 to 0.64) or patients with heart failure (OR 0.30, 95% CI 0.17 to 0.52). Patients evolving non-Q wave infarctions were older and had increased comorbidity counts and trends toward increased mortality. Angioplasty was chosen less for patients > or = 65 years old (p = 0.02); angioplasty and coronary artery bypass graft surgery were performed less in patients > or = 70 years old (p = 0.02). Patients treated invasively had lower mortality rates than those treated medically (p < 0.02). CONCLUSIONS: The use of thrombolytic agents and invasive treatment plans declined with age, and mortality increased with age. Trends toward increased mortality occurred with non-Q wave infarctions and race other than Caucasian.

Comparative antibody response in harbour and grey seals naturally infected by a morbillivirus.

The antibody response of free-ranging harbour and grey seals, naturally infected by a morbillivirus, was assessed using a virus neutralizing test and a radio-immunoprecipitation assay. The prevalence of antibody was similar between species, however, grey seals had significantly higher virus neutralizing titers. Serum from clinically healthy grey seals precipitated the nucleocapsid (N) protein along with the hemagglutinin (H) and fusion (F) glycoproteins. By contrast, significantly fewer harbour seal sera precipitated the envelope glycoproteins and responses were weaker than those of grey seals. One harbour seal with acute morbillivirus pneumonia, and two with encephalitis precipitated only the N protein. Serum from four harbour seals with encephalitis weakly recognized the envelope glycoproteins. Thus, the antibody response of grey seals appears more competent than that of harbour seals with respect to morbillivirus antigens. We speculate that this difference between the species may be an important determinant of morbillivirus susceptibility.

Epizootiology of morbillivirus infection in harp, hooded, and ringed seals from the Canadian Arctic and western Atlantic.

Using a virus neutralization technique, we found phocine distemper virus (PDV) antibody in 130 (83% of 157) harp seals (Phoca groenlandica) from the western North Atlantic sampled between 1988 and 1993 inclusive. In contrast, only 44 (24% of 185) hooded seals (Cystophora cristata) had antibodies against PDV even though they were sympatric with harp seals and were sampled over a similar period, from 1989 to 1994 inclusive. Antibodies occurred in 106 (41%) of 259 ringed seals (Phoca hispida); this prevalence was higher than expected given the solitary behavior and territoriality characteristic of this species. Seropositive ringed seals were found at each of seven locations across Arctic Canada from Baffin Bay to Amundsen Gulf at which samples were collected between 1992 and 1994. However, the prevalence of infection was highest where ringed seals are sympatric with harp seals in the eastern Canadian Arctic.

Radiation hepatology of the rat: association of the production of prostacyclin with radiation-induced hepatic fibrosis.

The hypothesis that hepatic fibrosis is preceded by inflammation and formation of prostanoids from arachidonic acid liberated from damaged cell membranes was investigated. Liver slices were prepared using a Krumdieck precision tissue slicer from sham-irradiated rats or from rats whose livers had been irradiated with 25 Gy 137Cs gamma rays in which injury was allowed to develop in vivo for 6 to 55 days. Unused portions of the liver were analyzed for hydroxyproline content to determine hepatic fibrosis. A unique organ culture system was used to incubate liver slices for 2 h. Secretion into the incubation medium of aspartate aminotransferase and 6-keto prostaglandin F1 alpha were measured to quantify damage to the hepatocyte membrane and production of prostacyclin, respectively. A threefold increase in the concentration of 6-keto prostaglandin F1 alpha in the medium was evident by 13 days after irradiation. This elevated concentration of 6-keto prostaglandin F1 alpha persisted for the remainder of the study and preceded fibrosis, as measured by liver hydroxyproline concentration, and hepatocyte membrane damage, as measured by release of aspartate aminotransferase into the incubation medium or plasma. We therefore suggest that, in the non-generating liver, damage and breakdown of nonparenchymal liver cell membrane is the principal source of 6-keto prostaglandin F1 alpha. These results are also compatible with the supposition that inflammation and release of arachidonic acid metabolites are one of the early biochemical events leading to hepatic fibrosis. How the release of arachidonic acid metabolites might initiate and sustain radiation-induced fibrosis is discussed. An explanation for the difference in liver fibrosis induced by chemicals and radiation is also presented.

Identifying complications and low provider adherence to normative practices using administrative data.

OBJECTIVE: This study investigated whether unexpected length of stay (LOS) could be used as an indicator to identify hospital patients who experienced complications or whose care exhibited low adherence to normative practices. DATA SOURCES AND STUDY SETTING: We analyzed 1,477 cases admitted for one of three medical conditions. All cases were discharged from one of nine participating Department of Veterans Affairs (VA) hospitals from October 1987 through September 1989. Analyses used administrative data and information abstracted through chart reviews that included severity of illness indicators, complications, and explicit process of care criteria reflecting adherence to normative practices. STUDY DESIGN: We developed separate multiple linear regression models for each disease using LOS as the dependent measure and variables that could be assumed present at the time of admission as explanatory variables. Unexpectedly long LOS (i.e., discharges with high residuals) was used to target complications and unexpectedly short LOS was used to target cases whose care might have exhibited low adherence to normative practices. Information gleaned from chart reviews served as the gold standard for determining actual complications and low adherence. PRINCIPAL FINDINGS: Analyses of administrative data showed that unexpectedly long LOS identified complications with sensitivities ranging from 40 through 62 percent across the three conditions. Positive predictive values all were at greater than chance levels (p < .05). This represented substantial improvement over identification of complications using ICD-9-CM codes contained in the administrative database where sensitivities were from 26 through 39 percent. Unexpectedly short LOS identified low provider adherence with sensitivities ranging from 33 through 45 percent with positive predictive values all above chance levels (p < .05). The addition to the LOS models of chart-based severity of illness information helped explain LOS, but failed to facilitate identification of complications or low adherence beyond what was accomplished using administrative data. CONCLUSIONS: Administrative data can be used to target cases when seeking to identify complications or low provider adherence to normative practices. Targeting can be accomplished through the creation of indirect measures based on unexpected LOS. Future efforts should be devoted to validating unexpected LOS as a hospital-level quality indicator. RELEVANCE/IMPACT: Scrutiny of unexpected LOS holds promise for enhancing the usefulness of administrative data as a resource for quality initiatives.

Epizootiology of morbillivirus infection in North American harbor seals (Phoca vitulina) and gray seals (Halichoerus grypus).

A longitudinal study of morbillivirus infection among harbor (Phoca vitulina) and gray (Halichoerus grypus) seals on the Atlantic coast of North America was carried out between 1980 and 1994. Serology also was carried out on harbor seals from the Pacific northwest coast collected in 1992 and 1993. The prevalence of morbillivirus neutralizing antibodies was significantly (P < 0.0001) higher in gray (73%, n = 296) than in harbor seals (37%, n = 387) from the Atlantic. Titers were significantly (P < 0.0001) higher against phocine distemper (PDV) compared to any other morbillivirus. Antibodies were not detected in serum from Pacific harbor seals. During the winter of 1991 to 1992 an epizootic occurred among harbor seals on the northeast coast of the United States. The event was characterized by an increase in strandings and by a significant (P = 0.001) increase in PDV antibody prevalence to 83% (n = 36) in seals stranded that winter. Morbillivirus lesions and antigen were observed in six animals found stranded from southern Maine to Long Island, New York (USA), between November 1991 and April 1992. In addition, morbillivirus encephalitis was detected in tissues from a harbor seal that stranded in 1988. Enzootic infection appeared to be present in both seal species, although with a different prevalence of disease. We propose that enzootic infection among gray seals is facilitated by population size, high annual recruitment and innate resistance to clinical disease. Infection may be maintained in the smaller harbor seal population through casual contact with gray seals.