Nosocomial infections and their relationship to non-traditional risk factors in a medical intensive care unit

Background. Nosocomial infections are a source of concern for many hospitals in the United States and worldwide. These infections are associated with increased morbidity, mortality and hospital costs. Nosocomial infections occur in ICUs at a rate which is five times greater than those in general wards. Understanding the reasons for the higher rates can ultimately help reduce these infections. The literature has been weak in documenting a direct relationship between nosocomial infections and non-traditional risk factors, such as unit staffing or patient acuity.^ Objective. To examine the relationship, if any, between nosocomial infections and non-traditional risk factors. The potential non-traditional risk factors we studied were the patient acuity (which comprised of the mortality and illness rating of the patient), patient days for patients hospitalized in the ICU, and the patient to nurse ratio.^ Method. We conducted a secondary data analysis on patients hospitalized in the Medical Intensive Care Unit (MICU) of the Memorial Hermann- Texas Medical Center in Houston during the months of March 2008- May 2009. The average monthly values for the patient acuity (mortality and illness Diagnostic Related Group (DRG) scores), patient days for patients hospitalized in the ICU and average patient to nurse ratio were calculated during this time period. Active surveillance of Bloodstream Infections (BSIs), Urinary Tract Infections (UTIs) and Ventilator Associated Pneumonias (VAPs) was performed by Infection Control practitioners, who visited the MICU and performed a personal infection record for each patient. Spearman's rank correlation was performed to determine the relationship between these nosocomial infections and the non-traditional risk factors.^ Results. We found weak negative correlations between BSIs and two measures (illness and mortality DRG). We also found a weak negative correlation between UTI and unit staffing (patient to nurse ratio). The strongest positive correlation was found between illness DRG and mortality DRG, validating our methodology.^ Conclusion. From this analysis, we were able to infer that non-traditional risk factors do not appear to play a significant role in transmission of infection in the units we evaluated.^

The effects of respiratory ailments and income on depression in a nationally representative sample

Asthma, chronic obstructive pulmonary disorder, sinusitis and hay fever have previously been documented as risk factors for future depression in a wide variety of populations. Likewise, belonging to a higher income category has been found to place a person at risk for any type of depression. This study investigates whether an interactive effect between personal income and the presence of any of the four aforementioned respiratory illnesses contribute to an increased risk for depression. Using the National Health and Nutrition Health Examination Survey cross-sectional survey for 2005-2006, analysis of an interaction term for each illness in the presence of confounding factors such as age, smoking status, past or present diagnosis of diabetes, coronary heart disease and heart attack was made within six distinct racial/ethnic and sex subgroups. Generally, interaction terms were found to be non-significant in nature, except hay fever and COPD where in a few subgroups where the interaction term conferred a protective or risk influence depending on the subgroup analyzed. These findings are discussed in light of potential social costs of having certain respiratory illnesses by individuals in higher income categories and the effect of severity within each illness on the resulting risk or protective effect of the interaction term.^

BIOLOGICAL MECHANISMS AND CLINICAL IMPLICATIONS OF BCR-ABL-INDUCED MITOCHONDRIAL OXIDATIVE STRESS AND CELL SURVIVAL IN CHRONIC MYELOID LEUKEMIA

Chronic myeloid leukemia (CML), a myeloproliferative disorder, represents approximately 15-20% of all adult leukemia. The development of CML is clearly linked to the constitutively active protein-tyrosine kinase BCR-ABL, which is encoded by BCR-ABL fusion gene as the result of chromosome 9/22 translocation (Philadelphia chromosome). Previous studies have demonstrated that oxidative stress-associated genetic, metabolic and biological alterations contribute to CML cell survival and drug refractory. Mitochondria and NAD(P)H oxidase (NOX) are the major sources of BCR-ABL-induced cellular reactive oxygen species (ROS) production. However, it is still unknown how CML cells maintain the altered redox status, while escaping from the persistent oxidative stress-induced cell death. Therefore, elucidation of the mechanisms by which CML cells cope with oxidative stress will provide new insights into CML leukemogenesis. The major goal of this study is to identify the survival factors protecting CML cells against oxidative stress and develop novel therapeutic strategies to overcome drug resistance. Several experimental models were used to test CML cell redox status and cellular sensitivity to oxidative stress, including BCR-ABL inducible cell lines, BCR-ABL stably transformed cell lines and BCR-ABL-expressing CML blast crisis cells with differential BCL-XL/BCL-2 expressions. Additionally, an artificial CML cell model with heterogenic BCL-XL/BCL-2 expression was established to assess the correlation between differential survival factor expression patterns and cell sensitivity to Imatinib and oxidative stress. In this study, BCL-XL and GSH have been identified as the major survival factors responsive to BCR-ABL-promoted cellular oxidative stress and play a dominant role in regulating the threshold of oxidative stress-induced apoptosis. Cell survival factors BCL-XL and BCL-2 differentially protect mitochondria under oxidative stress. BCL-XL is an essential survival factor in preventing excessive ROS-induced cell death while BCL-2 seems to play a relatively minor role. Furthermore, the redox modulating reagent β-phenethyl isothiocyanate (PEITC) has been found to efficiently deplete GSH and induce potent cell killing effects in drug-resistant CML cells. Combination of PEITC with BCL-XL/BCL2 inhibitor ABT737 or suppression of BCL-XL by BCR-ABL inhibitor Gleevec dramatically sensitizes CML cells to apoptosis. These results have suggested that elevation of BCL-XL and cellular GSH are important for the development of CML, and that redox-directed therapy is worthy of further clinical investigations in CML.

The effect of chronic arthritis and hypertension on general well-being

The purpose of the investigation is to elucidate the effect of chronic symptomatic and asymptomatic disease, i.e. arthritis and hypertension, on general well-being, and to quantify the contribution that the duration of the disorder makes to this effect. The data is drawn from the National Health and Nutrition Examination Survey (NHANES I). The results show that arthritics do not have a significant effect on GWB scores while hypertension has a significantly negative impact on GWB. The most striking difference is seen between those without knowledge of hypertension and those recently diagnosed. This difference is attributed to the labeling effect on changes in perceived wellness. ^

The role of chronic irritation and inflammation in tumor promotion in CD-1 mice by petroleum middle distillates

An initiation-promotion bioassay in CD-1 mice was used to examine the role of chronic irritation and inflammation in tumor promotion by petroleum middle distillates. A representative hydrodesulfurized middle distillate (API 81-07) was selected as the test article. Test groups (54 mice per group) were initiated once with 50 ug of 7,12-dimethylbenzanthracene (DMBA). Promotion with API 81-07 consisted of twice weekly treatments for 25 weeks with either 25 ul, 50 ul, 50 ul + daily treatment with 15 ug dexamethasone, 50 ul + post-application washings, and 100 ul. Three mice from each group were sacrificed at 21 day intervals (24 total per group). The skin from interim sacrificed (IS) mice was examined histopathologically for tumor, acanthosis, hyperkeratosis, pseudo-epitheliomatous hyperplasia, epidermal crusting, and subacute inflammation. In-life observations included examination of all mice for erythema and edema for 8 weeks following the first promotion treatment. Tumor incident at study termination was as follows: 25 ul (45%), 50 ul (43%), 50 ul + dexamethasone (0%), 50 ul + washing (70%), and 100 ul (81%). An overall correlation of $>$0.90 between tumor incidence and group means for acanthosis and hyperkeratosis was observed in IS mice at all intervals. Correlations of $<$0.75 were observed for other group mean histopathological parameters and tumor incidence. The overall correlation of group mean erythema and edema with tumor incident was $>$0.90. The results of this study support the hypothesis that induction of a lasting, albeit mild, hyperplasia is an essential, but not sufficient requirement, for tumor promotion. Furthermore, subacute inflammation does not appear to be a significant factor in tumor promotion by petroleum middle distillates. However, inflammation may be a factor in tumor progression. ^

Comparison of medical care costs, utilization, and satisfaction of AIDS patients with and without home care

A sample of 157 AIDS patients 17 years of age or over were followed for six months from the date of hospital discharge to derive average total cost of medical care, utilization and satisfaction with care. Those referred for home care follow-up after discharge from the hospital were compared with those who did not receive home care.^ The average total cost of medical care for all patients was $34,984. Home care patient costs averaged \$29,614 while patients with no home care averaged $37,091. Private hospital patients had average costs of \$50,650 compared with $25,494 for public hospital patients. Hospital days for the six months period averaged 23.9 per patient for the no home care group and 18.5 days for home care group. Patient satisfaction with care was higher in the home care group than no home care group, with a mean score of 68.2 compared with 61.1.^ Other health services information indicated that 98% of the private hospital patients had insurance while only 2% of public hospital patients had coverage. The time between the initial date of diagnosis with AIDS and admission to the study was longer for private hospital patients, survival time over the study period was shorter, and the number of hospitalizations prior to entering the study was higher for private hospital patients. These results suggest that patients treated in the private hospital were sicker than public hospital patients, which may explain their higher average total cost. Statistical analyses showed that cost and utilization have no significant relationship with home care or no home care when controlling for indicators of the severity of illness and treatment in public or private hospital.^ In future studies, selecting a matched group of patients from the same hospital and following them for nine months to one year would be helpful in making a more realistic comparison of the cost effectiveness of home care. ^

MEDICAL CARE UTILIZATION IN TIME AMONG ELDERLY MEDICARE ENROLLEES IN AN HMO

Investigation into the medical care utilization of elderly Medicare enrollees in an HMO (Kaiser - Portland, Oregon): The specific research topics are: (1) The utilization of medical care by selected determinants such as: place of service, type of service, type of appointment, physician status, physician specialty and number of associated morbidities. (2) The attended prevalence of 3 chronic diseases: hypertension, diabetes and arthritis in addition to pneumonias as an example of acute diseases. The selection of these examples was based on their importance in morbidity/or mortality results among the elderly. The share of these diseases in outpatient and inpatient contacts was examined as an example of the relation between morbidity and medical care utilization. (3) The tendency of individual utilization patterns to persist in subsequent time periods. The concept of contagion or proneness was studied in a period of 2 years. Fitting the negative binomial and the Poisson distributions was applied to the utilization in the 2nd year conditional on that in the 1st year as regards outpatient and inpatient contacts.^ The present research is based on a longitudinal study of 20% random sample of elderly Medicare enrollees. The sample size is 1683 individuals during the period from August 1980-December 1982.^ The results of the research were: (1) The distribution of contacts by selected determinants did not reveal a consistent pattern between sexes and age groups. (2) The attended prevalence of hypertension and arthritis showed excess prevalence among females. For diabetes and pneumonias no female excess was noticed. Consistent increased prevalence with increasing age was not detected.^ There were important findings pertaining to the relatively big share of the combined 3 chronic diseases in utilization. They accounted for 20% of male outpatient contacts vs. 25% of female outpatients. For inpatient contacts, they consumed 20% in case of males vs. 24% in case of females. (3) Finding that the negative binomial distribution fit the utilization experience supported the research hypothesis concerning the concept of contagion in utilization. This important finding can be helpful in estimating liability functions needed for forecasting future utilization according to previous experience. Such information has its relevance to organization, administration and planning for medical care in general. (Abstract shortened with permission of author.) ^

A STUDY OF ILLNESS AND RESERVOIRS ASSOCIATED WITH GIARDIA LAMBLIA IN RURAL EGYPT

A longitudinal investigation of the health effects and reservoirs of Giardia lamblia was undertaken in forty households located in a rural Nile Delta region of Egypt. Stool specimens obtained once weekly for six months from two to four year old children were cyst or trophozoite-positive in 42 percent of the 724 examined. The mean duration of excretion in all but one Giardia-negative child was seven and one-half weeks with a range of one to 17 weeks. Clinical symptoms of illness were frequently observed within a month before or after Giardia excretion in stool of children, but a statistical inference of association was not demonstrated.^ Seventeen percent of 697 specimens obtained from their mothers was Giardia-positive for a mean duration of four weeks and a range of one to 18 weeks. Mothers were observed to excrete Giardia in stool less frequently during pregnancy than during lactation.^ Nine hundred sixty-two specimens were collected from 13 species of household livestock. Giardia was detected in a total of 22 specimens from cows, goats, sheep and one duck. Giardia cysts were detected in three of 899 samples of household drinking water.^ An ELISA technique of Giardia detection in human and animal stool was field tested under variable environmental conditions. The overall sensitivity of the assay of human specimens was 74 percent and specificity was 97 percent. These values for assay of animal specimens were 82 percent and 98 percent, respectively.^ Surface antigen studies reported from the NIH Laboratory of Parasitic Diseases show that antigens of three Egyptian human isolates are different from each other and from most other isolates against which they were tested.^ The ubiquity of human and animal fecal contamination combined with estimates of ill days per child per year in this setting are substantial arguments for the introduction of a suggested mass parasite control program to intervene in the cyclical transmission of agents of enteric disease. ^

THE USE OF ARM CIRCUMFERENCE FOR SIMPLIFIED SCREENING FOR MALNUTRITION BY MINIMALLY TRAINED HEALTH WORKERS

Because of its simplicity and low cost, arm circumference (AC) is being used increasingly in screening for protein energy malnutrition among pre-school children in many parts of the developing world, especially where minimally trained health workers are employed. The objectives of this study were as follows: (1) To determine the relationship of the AC measure with weight for age and weight for height in the detection of malnutrition among pre-school children in a Guatemalan Indian village. (2) To determine the performance of minimally trained promoters under field conditions in measuring AC, weight and height. (3) To describe the practical aspects of taking AC measures versus weight, age and height.^ The study was conducted in San Pablo La Laguna, one of four villages situated on the shores of Lake Atitlan, Guatemala, in which a program of simplified medical care was implemented by the Institute for Nutrition for Central America and Panama (INCAP). Weight, height, AC and age data were collected for 144 chronically malnourished children. The measurements obtained by the trained investigator under the controlled conditions of the health post were correlated against one another and AC was found to have a correlation with weight for age of 0.7127 and with weight for height of 0.7911, both well within the 0.65 to 0.80 range reported in the literature. False positive and false negative analysis showed that AC was more sensitive when compared with weight for height than with weight for age. This was fortunate since, especially in areas with widespread chronic malnutrition, weight for height detects those acute cases in immediate danger of complicating illness or death. Moreover, most of the cases identified as malnourished by AC, but not by weight for height (false positives), were either young or very stunted which made their selection by AC better than weight for height. The large number of cases detected by weight for age, but not by AC (false negative rate--40%) were, however, mostly beyond the critical age period and had normal weight for heights.^ The performance of AC, weight for height and weight for age under field conditions in the hands of minimally trained health workers was also analyzed by correlating these measurements against the same criterion measurements taken under ideally controlled conditions of the health post. AC had the highest correlation with itself indicating that it deteriorated the least in the move to the field. Moreover, there was a high correlation between AC in the field and criterion weight for height (0.7509); this correlation was almost as high as that for field weight for height versus the same measure in the health post (0.7588). The implication is that field errors are so great for the compounded weight for height variable that, in the field, AC is about as good a predictor of the ideal weight for height measure.^ Minimally trained health workers made more errors than the investigator as exemplified by their lower intra-observer correlation coefficients. They consistently measured larger than the investigator for all measures. Also there was a great deal of variability between these minimally trained workers indicating that careful training and followup is necessary for the success of the AC measure.^ AC has many practical advantages compared to the other anthropometric tools. It does not require age data, which are often unreliable in these settings, and does not require sophisticated subtraction and two dimensional table-handling skills that weight for age and weight for height require. The measure is also more easily applied with less disturbance to the child and the community. The AC tape is cheap and not easily damaged or jarred out of calibration while being transported in rugged settings, as is often the case with weight scales. Moreover, it can be kept in a health worker's pocket at all times for continual use in a widespread range of settings. ^

MEASURING THE EFFECT OF ILLNESS ON THE EXPECTED REMAINING SERVICE TIME FOR THE ACTIVE DUTY ARMY: A LIFE TABLE APPROACH

A life table methodology was developed which estimates the expected remaining Army service time and the expected remaining Army sick time by years of service for the United States Army population. A measure of illness impact was defined as the ratio of expected remaining Army sick time to the expected remaining Army service time. The variances of the resulting estimators were developed on the basis of current data. The theory of partial and complete competing risks was considered for each type of decrement (death, administrative separation, and medical separation) and for the causes of sick time.^ The methodology was applied to world-wide U.S. Army data for calendar year 1978. A total of 669,493 enlisted personnel and 97,704 officers were reported on active duty as of 30 September 1978. During calendar year 1978, the Army Medical Department reported 114,647 inpatient discharges and 1,767,146 sick days. Although the methodology is completely general with respect to the definition of sick time, only sick time associated with an inpatient episode was considered in this study.^ Since the temporal measure was years of Army service, an age-adjusting process was applied to the life tables for comparative purposes. Analyses were conducted by rank (enlisted and officer), race and sex, and were based on the ratio of expected remaining Army sick time to expected remaining Army service time. Seventeen major diagnostic groups, classified by the Eighth Revision, International Classification of Diseases, Adapted for Use In The United States, were ranked according to their cumulative (across years of service) contribution to expected remaining sick time.^ The study results indicated that enlisted personnel tend to have more expected hospital-associated sick time relative to their expected Army service time than officers. Non-white officers generally have more expected sick time relative to their expected Army service time than white officers. This racial differential was not supported within the enlisted population. Females tend to have more expected sick time relative to their expected Army service time than males. This tendency remained after diagnostic groups 580-629 (Genitourinary System) and 630-678 (Pregnancy and Childbirth) were removed. Problems associated with the circulatory system, digestive system and musculoskeletal system were among the three leading causes of cumulative sick time across years of service. ^

THE BACON CHOW STUDY: THE RELATIONSHIP BETWEEN INFECTIOUS ILLNESS AND GROWTH OF INFANTS

Multiple dietary deficiencies and high rates of infectious illness are major health problems leading to malnutrition and limitation of growth of children in developing countries. Longitudinal studies which provide information on illness incidence and growth velocity are needed in order to untangle the complex interrelationship between nutrition, illness and growth. From 1967 to 1973, researchers led by Dr. Bacon Chow of the Johns Hopkins University School of Hygiene undertook a quasi-experimental prospective study in Suilin Township, Taiwan to determine the effects of a nutritional supplement to the diets of pregnant and lactating women on the growth, development and resistance to disease of their offspring. This dissertation presents results from the analysis of infant morbidity and postnatal growth.^ Maternal nutritional supplementation has no apparent effect on the postnatal growth or morbidity of infants. Significant sex differences exist in growth response to illness and in illness susceptibility. Male infants have more diarrhea and upper respiratory illness. Respiratory illness is positively associated with growth rate in weight in the first semester of life. Diarrhea is significantly negatively associated with growth in length in the second semester. Small-for-date infants are more susceptible to illness in general and have a different pattern of growth response than large-for-date infants.^ Principal components analysis of illness data is shown to be an effective technique for making more precise use of ambiguous morbidity data. Multiple regression with component scores is an accurate method for estimating variance in growth rate predicted by indepenent illness variables. A model is advanced in which initial postnatal growth rate determines subsequent susceptibility to nutritional stress and infection. Initial growth rate is a function of prenatal nutrition, but is not significantly affected by maternal supplementation during gestation or lactation. Critical evaluation is made of nutritional supplementation programs which do not afford disease control.^

INFECTION: ITS ECOLOGICAL DETERMINANTS AMONG CHILDREN IN NORTHERN CHILE

In developing countries, infection and malnutrition, and their interaction effects, account for the majority of childhood deaths and chronic deficits in growth and development. To promote child health, the causal determinants of infection and malnutrition and cost-effective interventions must be identified. To this end, medical examinations of 988 children (age two weeks to 14 years) living at three altitudes (coastal < 300m; sierra (TURN) 3,000m; and altiplano > 4,000m) in Chile's northermost Department of Arica revealed that 393 (40%) of the youngsters harbored one or more infections. When sorted by region and ethnicity, indigenous children of the highlands had infection rates 50% higher than children of Spanish descent living near the coast.^ An ecological model was developed and used to examine the causal path of infection and measure the effect of single and combined environmental variables. Family variables significantly linked to child health included maternal health, age and education. Significant child determinants of infection included the child's nutrient intake and medical history. When compared to children well and free of disease, infected youngsters reported a higher incidence of recent illness and a lower intake of basic foodstuffs. Traditional measures of child health, e.g. birth condition, weaning history, maternal fertility, and family wealth, did not differentiate between well and infected children.^ When height, weight, arm circumference, and subcapular skinfold measurements were compared, infected children, regardless of age, had smaller arm circumferences, the statistical difference being the greatest for males, age nine to eleven. Height and weight, the traditional growth indices, did not differentiate between well and infected groups.^ Infection is not determined by a single environmental factor or even a series of variables. Child health is ecological in nature and cannot be improved independent of changes in the environment that surrounds the child. To focus on selected child health needs, such as feeding programs or immunization campaigns, without simultaneously attending to the environment from which the needs arose is an inappropriate use of time, personnel, and money. ^