Diagnosis and management of pulmonary infection due to Rhodococcus equi.

BACKGROUND: Rhodococcus equi is a recognized cause of disease in humans, especially in individuals who are immunocompromised. Because diphtheroids are regarded as part of normal respiratory flora, the importance of R. equi as a pulmonary pathogen may not be fully appreciated and its prevalence may be underestimated. Most treatment recommendations for R. equi infection were established before antiretroviral drugs became available for human immunodeficiency virus/AIDS therapy, and therapeutic strategies may need to be updated. OBJECTIVES: To review the role of R. equi as a cause of pulmonary infection; to highlight its importance for clinicians and microbiologists; and to challenge current approaches to treatment, whether in immunodeficient or immunocompetent individuals. SOURCES: A PubMed search using combinations of the following terms: 'Rhodococcus (automatically including Corynebacterium) equi' AND 'pneumonia' OR 'pulmonary' infection, then cross-checking references in the resulting cases, case series and reviews. CONTENT: We provide a review that details the challenges in the diagnosis, microbiology and pathogenesis of pulmonary infection caused by R. equi and the options for treatment. IMPLICATIONS: Ten to 14 days of treatment may be effective for pneumonia due to R. equi. Our review suggests that longer courses of therapy are needed for cavitary lesions and lung masses. However, recommendations for excessively prolonged treatment of all pulmonary infections arose during a time when many cases occurred in individuals with AIDS and before effective antiretroviral therapy was available. We suggest that the rationale for prolonged therapy with multiple antibiotics needs to be re-evaluated.

Drug repurposing to treat asthma and allergic disorders: Progress and prospects.

Allergy and atopic asthma have continued to become more prevalent in modern society despite the advent of new treatments, representing a major global health problem. Common medications such as antihistamines and steroids can have undesirable long-term side-effects and lack efficacy in some resistant patients. Biologic medications are increasingly given to treatment-resistant patients, but they can represent high costs, complex dosing and management, and are not widely available around the world. The field needs new, cheap, and convenient treatment options in order to bring better symptom relief to patients. Beyond continued research and development of new drugs, a focus on drug repurposing could alleviate this problem by repositioning effective and safe small-molecule drugs from other fields of medicine and applying them toward the treatment for asthma and allergy. Herein, preclinical models, case reports, and clinical trials of drug repurposing efficacy in allergic disease are reviewed. Novel drugs are also proposed for repositioning based on their mechanism of action to treat asthma and allergy. Overall, drug repurposing could become increasingly important as a way of advancing allergy and atopic asthma therapy, filling a need in treatment of patients today.

Prenatal phthalate exposure and reduced masculine play in boys.

Foetal exposure to antiandrogens alters androgen-sensitive development in male rodents, resulting in less male-typical behaviour. Foetal phthalate exposure is also associated with male reproductive development in humans, but neurodevelopmental outcomes have seldom been examined in relation to phthalate exposure. To assess play behaviour in relation to phthalate metabolite concentration in prenatal urine samples, we recontacted participants in the Study for Future Families whose phthalate metabolites had been measured in mid-pregnancy urine samples. Mothers completed a questionnaire including the Pre-School Activities Inventory, a validated instrument used to assess sexually dimorphic play behaviour. We examined play behaviour scores (masculine, feminine and composite) in relationship to (log(10)) phthalate metabolite concentrations in mother's urine separately for boys (N = 74) and girls (N = 71). Covariates (child's age, mother's age and education and parental attitude towards atypical play choices) were controlled using multivariate regression models. Concentrations of dibutyl phthalate metabolites, mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) and their sum, were associated with a decreased (less masculine) composite score in boys (regression coefficients -4.53,-3.61 and -4.20, p = 0.01, 0.07 and 0.04 for MnBP, MiBP and their sum respectively). Concentrations of two urinary metabolites of di(2-ethylhexyl) phthalate (DEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and the sum of these DEHP metabolites plus mono(2-ethylhexyl) phthalate were associated with a decreased masculine score (regression coefficients -3.29,-2.94 and -3.18, p = 0.02, 0.04 and 0.04) for MEHHP, MEOHP and the sum respectively. No strong associations were seen between behaviour and urinary concentrations of any other phthalate metabolites in boys, or between girls' scores and any metabolites. These data, although based on a small sample, suggest that prenatal exposure to antiandrogenic phthalates may be associated with less male-typical play behaviour in boys. Our findings suggest that these ubiquitous environmental chemicals have the potential to alter androgen-responsive brain development in humans.

Benefits and pitfalls of pooling datasets from comparable observational studies: combining US and Dutch nursing home studies.

Different research groups sometimes carry out comparable studies. Combining the data can make it possible to address additional research questions, particularly for small observational studies such as those frequently seen in palliative care research. We present a systematic approach to pool individual subject data from observational studies that addresses differences in research design, illustrating the approach with two prospective observational studies on treatment and outcomes of lower respiratory tract infection in US and Dutch nursing home residents. Benefits of pooling individual subject data include enhanced statistical power, the ability to compare outcomes and validate models across sites or settings, and opportunities to develop new measures. In our pooled dataset, we were able to evaluate treatments and end-of-life decisions for comparable patients across settings, which suggested opportunities to improve care. In addition, greater variation in participants and treatments in the combined dataset allowed for subgroup analyses and interaction hypotheses, but required more complex analytic methods. Pitfalls included the large amount of time required for equating study procedures and variables and the need for additional funding.

Dementia severity, decline and improvement after a lower respiratory tract infection.

OBJECTIVE: To assess decline and improvement in functional characteristics, cognition and restraint use after a lower respiratory tract infection (LRI) and describe variation by dementia severity. DESIGN: Two prospective cohort studies. SETTING: Nursing homes in the Netherlands and in Missouri, USA. PARTICIPANTS: 227 Dutch and 396 Missouri nursing home residents with dementia and LRI who were treated with antibiotics. MEASUREMENTS: We compared functional characteristics (Activities of Daily Living [ADL], bedfast status, pressure ulcers, incontinence), cognition and restraint use 3 months after an LRI with status 1 to 2 weeks before diagnosis. RESULTS: Residents with LRI frequently declined on all measures, but many also improved, including those with severe dementia. On the measures where residents could still decline further, residents with severe dementia showed higher variability than residents with less severe dementia. This was most obvious for bedfast status and restraint use. CONCLUSIONS: Compared with less severely demented residents, residents with severe dementia showed more decline on measures where they still had room for change. However, on these measures, residents with severe dementia also improved more often. LRI does not necessarily lead to deterioration even in individuals with severe dementia.

[Treatment of pneumonia in nursing home residents with severe dementia: for residents with poor prognosis, a more reserved approach in The Netherlands and more active treatment in the United States]. / Behandeling van pneumonie bij verpleeghuispatiënten met ernstige dementie: terughoudender beleid in Nederland en actiever beleid in de verenigde Staten naarmate de prognose ongunstiger is.

OBJECTIVE: To describe differences in the treatment of pneumonia and in the association of treatment with prognosis in Dutch and American nursing home patients with late-stage dementia. Design. Prospective studies in The Netherlands and the American state of Missouri. METHOD: In 61 Dutch nursing homes and 36 in Missouri, severely demented patients with pneumonia were included in the periods October 1996-July 1998 and August 1995-September 1998 respectively. Data was collected on their state of health, comorbidity, symptoms of pneumonia and treatment aspects such as antibiotic use, hospital admission and relief of symptoms. Comparisons were made between treatments in both countries and between groups of patients with a similar probability of mortality within 2 weeks. RESULTS: A total of 328 Dutch and 280 American patients were selected. Antibiotics were more frequently withheld in The Netherlands (in 33% of patients) than in Missouri (24%). Differences in antibiotic use were more pronounced in patients with a poor prognosis (56% versus 15%). Dutch patients were more frequently dehydrated but were less likely to receive rehydration therapy than American patients, with a larger difference in patients with a poor prognosis (2% versus 63%). Treatments to relieve symptoms that were provided more often in patients with a poor prognosis (in 20-26%) were: oxygen (both countries), and in The Netherlands also opiates, and hypnotics, sedatives or anxiolytics. CONCLUSION: In The Netherlands, curative treatment was frequently withheld in patients with severe dementia and pneumonia, and even more frequently when the prognosis was poorer. Conversely, treatment in Missouri was more active in patients with a poor prognosis. Despite more frequent palliative treatment goals in The Netherlands, treatments to relieve symptoms were provided infrequently and inconsistent with this approach. These insights may be helpful for decision-making in the treatment of pneumonia in patients with severe dementia.

Predicting mortality in nursing home residents with lower respiratory tract infection: The Missouri LRI Study.

CONTEXT: Lower respiratory tract infection (LRI) is a leading cause of mortality and hospitalization in nursing home residents. Treatment decisions may be aided by a clinical prediction rule that identifies residents at low and high risk of mortality. OBJECTIVE: To identify patient characteristics predictive of 30-day mortality in nursing home residents with an LRI. DESIGN, SETTING, AND PATIENTS: Prospective cohort study of 1406 episodes of LRI in 1044 residents of 36 nursing homes in central Missouri and the St Louis, Mo, area between August 15, 1995, and September 30, 1998. MAIN OUTCOME MEASURE: Thirty-day all-cause mortality. RESULTS: Thirty-day mortality was 14.7% (n = 207). In a logistic analysis, using generalized estimating equations to adjust for clustering, we developed an 8-variable model to predict 30-day mortality, including serum urea nitrogen, white blood cell count, body mass index, pulse rate, activities of daily living status, absolute lymphocyte count of less than 800/microL (0.8 x 10(9)/L), male sex, and deterioration in mood over 90 days. In validation testing, the model exhibited reasonable discrimination (c =.76) and calibration (nonsignificant Hosmer-Lemeshow goodness-of-fit statistic, P =.54). A point score based on this model's variables fit to the entire data set closely matched observed mortality. Fifty-two percent of residents had low (score of 0-4) or relatively low (score of 5-6) predicted 30-day mortality, with 2.2% and 6.2% actual mortality, respectively. CONCLUSIONS: Our model distinguishes nursing home residents at relatively low risk for mortality due to LRI. If independently validated, our findings could help physicians identify nursing home residents in need of different therapeutic approaches for LRI.

Clinical findings associated with radiographic pneumonia in nursing home residents.

OBJECTIVE: Subtle presentation and the frequent lack of on-site physicians complicate the diagnosis of pneumonia in nursing home residents. We sought to identify clinical findings (signs, symptoms, and simple laboratory studies) associated with radiographic pneumonia in sick nursing home residents. STUDY DESIGN: This was a prospective cohort study. POPULATION: The residents of 36 nursing homes in central Missouri and the St. Louis area with signs or symptoms suggesting a lower respiratory infection were included. OUTCOME MEASURED: We compared evaluation findings by project nurses with findings reported from chest radiographs. RESULTS: Among 2334 episodes of illness in 1474 nursing home residents, 45% of the radiograph reports suggested pneumonia (possible=12%; probable or definite = 33%). In 80% of pneumonia episodes, subjects had 3 or fewer respiratory or general symptoms. Eight variables were significant independent predictors of pneumonia (increased pulse, respiratory rate =30, temperature =38 degrees C, somnolence or decreased alertness, presence of acute confusion, lung crackles on auscultation, absence of wheezes, and increased white blood count). A simple score (range = -1 to 8) on the basis of these variables identified 33% of subjects (score > or =3) with more than 50% probability of pneumonia and an additional 24% (score of 2) with 44% probability of pneumonia. CONCLUSIONS: Pneumonia in nursing home residents is usually associated with few symptoms. Nonetheless, a simple clinical prediction rule can identify residents at very high risk of pneumonia. If validated in other studies, physicians could consider treating such residents without obtaining a chest radiograph.

The Zipper: a method for using personal identifiers to link data while preserving confidentiality.

OBJECTIVE: This report describes a method for linking separate confidential data sets that contain personal identifying information while preserving required anonymity. METHODS: Research data were linked with child abuse and neglect (CAN) report data by an independent "safe" analyst using an identical set of unique identifier codes assigned to each case in both data sets after all personal identifiers had been removed. RESULTS: The research team never learned CAN report status of individuals, the state agency never saw the research data, and the desired analyses were completed using the merged data set. CONCLUSIONS: The method was successfully used to merge data from separate sources without divulging confidential information.

A prospective investigation of the impact of smoking bans on tobacco cessation and relapse.

BACKGROUND AND OBJECTIVES: To examine the long term impact of workplace smoking bans on employee smoking cessation and relapse. Over three years we studied a total of 1033 current or former smokers (intervention group) employed in smoke-free hospitals and 816 current or former smokers (comparison group) employed in non-smoke-free workplaces. The design of this natural experiment is a prospective cohort study. We randomly selected both hospitals and employees from 12 strata based on hospital size and state tobacco regulations, and sampled employees in the same communities. Main outcome measures were post-ban quit ratio and relapse rate. RESEARCH DESIGN: Between groups comparisons were conducted using the Cochran-Mantel-Haenszel statistic for general association, stratified Cox proportional hazards models, and the CMH analysis of variance statistic based on ranks. McNemar's test and the sign test were used to test for changes over time within each group. RESULTS: Differences in the post-ban quit ratio were observed between intervention and comparison groups (p < or = 0.02). For employees whose bans were implemented at least seven years before survey, the post-ban quit ratio was estimated at 0.256, compared with 0.142 for employees in non-smoke-free workplaces (p = 0.02). After controlling for a variety of factors, time to quit smoking was shorter for the hospital employees (p < 0.001), with an overall relative risk of quitting of 2.3. Contrary to expectations, relapse rates were similar between the groups. CONCLUSION: Employees in workplaces with smoking bans have higher rates of smoking cessation than employees where smoking is permitted, but relapse is similar between these two groups of employees. The results of this investigation have international applicability for policy makers, clinicians, employers, and employees. Countries should review smoking policies in workplaces in light of their own smoking patterns and efforts to deal with environmental tobacco smoke.

The natural history of the use of healthcare information by women with breast cancer: a conceptual model.

The overall goal of our research agenda is to contribute to improved quality of healthcare by identifying factors that foster or inhibit the use of healthcare information by patients to make informed healthcare decisions. We propose to study the natural history of the use of healthcare information by women with breast cancer to support decisions about health care. To do so in this paper we propose a conceptual model developed based on an extensive literature review and critique that describes patients' health information use over the disease course. It will guide our further investigation of the complex relationships among patients' personal circumstances, the progress of their medical treatment, and their satisfaction and empowerment as informed decision-makers. The model will help policy makers and health professionals identify the best means to provide patients with useful information, and help all stakeholders in health care acquire information needed to improve healthcare quality.

An investigation of social and class differences in very-low birth weight outcomes: a continuing public health concern.

The objective of this study was to examine the relationship of nonmedical factors, including socioeconomic status, social class, education, race, and social support, to low birth weight. In a case-control study of all resident very-low-birth-weight births between December 1, 1989, and March 31, 1991, mothers completed an extensive survey related to their experience of pregnancy, including prenatal and postnatal care. Cases were defined as very-low-birth-weight (VLBW) infants and were matched to moderately-low-birth-weight and normal-birth-weight infants in race, age, and maternal residence. The hypothesis that social and class factors are more predictive of low birth weight than medical factors alone for women without chronic health problems was supported. Although the degree of the association varies depending on birth weight outcome, race even though addressed through matching--continued to play an important role in birth outcomes. A comparison of logistic model performance with and without the inclusion of social factors indicated the importance these variables play in prediction of birth outcomes. This is one of the few studies undertaken that explicitly investigates impact of patient factors on medical care.

Mortality from lower respiratory infection in nursing home residents. A pilot prospective community-based study.

BACKGROUND: Lower respiratory infections (LRI) are an important cause of morbidity, mortality, and hospitalization of nursing home residents, yet treatment recommendations have primarily been based on the minority who are hospitalized. We sought to prospectively evaluate risk factors for mortality from LRI in community nursing home residents. METHODS: We studied residents of 10 central Missouri nursing homes (910 beds) from January 1994 to September 1994. Attending physicians authorized nurse evaluations of ill residents who showed symptoms of an LRI. Those residents who met the study definition of LRI received a more detailed assessment and follow ups at 30 and 90 days. RESULTS: The 231 evaluations identified 141 LRIs in 121 individuals. Sixteen (11%) residents died within 30 days of evaluation. The most important univariate predictor of 30-day mortality was severe activities of daily living (ADL) dependency (relative risk = 8.8, 95% confidence interval, 2.55-30.1). Several other clinical and laboratory findings were also significant predictors. In multivariable logistic regression, ADL dependency, respiratory rate, and pneumonia on chest radiograph independently predicted mortality; the model showed good discriminating ability (c = .83). CONCLUSIONS: For nursing home residents with LRI, ADL dependency is an important mortality predictor. Further research with a larger sample should lead to a useful prediction rule for outcome from nursing home-acquired LRI.

Implementing smoking bans in American hospitals: results of a national survey.

OBJECTIVES: To determine how well hospitals complied with the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) tobacco control standards, which required banning smoking in hospital buildings; to explore issues involved in developing and implementing smoking bans; and to ascertain the perceived success of the policies. DESIGN: Postal survey conducted January through June 1994. PARTICIPANTS: Stratified random sample of American hospitals surveyed by JCAHO (n = 1055). MAIN OUTCOME MEASURES: Enacting smoking policies more restrictive than the JCAHO standard; the respondent's judgment of the relative success of the hospital's smoking policy. RESULTS: More than 96% of hospitals complied with the smoking ban standard; 41.4% enacted policies that were more restrictive than required by JCAHO. Several characteristics were associated with exceeding JCAHO requirements: location in a "non-tobacco state"; having fewer than 100 beds; location in a metropolitan statistical area; having unionsed employees; and having no psychiatric or substance abuse unit, favour having the same tobacco policy in psychiatry and substance abuse units as the rest of the hospital. More than 95% of respondents viewed their hospital's policy as successful. The JCAHO requirements and concern for employees' health were the major forces influencing hospitals to go smoke-free. Negative employee morale and lack of acceptance by visitors and patients were the most commonly cited barriers to overcome when implementing smoke-free policies. CONCLUSIONS: Smoking bans were successfully implemented in American hospitals, with many restricting smoking beyond the JCAHO standard. Other industries wishing to follow hospitals' lead would be most likely to succeed in the context of a social norm favouring a smoking ban and regulation by an outside agency.

A framework for designing and implementing community benefit standards.

Increasingly, health care professionals and the public are asking questions about the role of the hospital in meeting community need including its not-for-profit tax status. This article reviews the community benefit literature, provides a framework for understanding how a hospital community benefit program was developed, and delineates through a structured case study the lessons learned from this experience. It provides the practitioner with a context in which other hospitals may replicate the program and gives researchers a substantive case study that may be used as the basis for the empirical testing of community benefit models. The authors also outline the many difficult issues faced by a typical community hospital as it attempted to examine and develop additional responses to community need.

Hospital smoking bans and employee smoking behavior: Results of a national survey.

OBJECTIVE: To examine the impact of workplace smoking bans on smoking behavior of employees. PARTICIPANTS: A total of 1469 current or former smokers (intervention group) employed in smoke-free hospitals and 920 current or former smokers (comparison group) employed in non-smoke-free workplaces were surveyed to determine smoking behavior. DESIGN: This cross-sectional study is part of a larger, ongoing prospective study. The study design was quasi-experimental. We randomly selected sites consisting of a hospital and a corresponding community. Furthermore, we randomly selected subjects from hospitals and their corresponding communities. MAIN OUTCOME MEASURES: Postban quit ratio and progression along the stages-of-change continuum. METHODS: The Cox proportional hazards model was used to compare the postban quit ratio between the intervention and comparison groups. The Cochran-Mantel-Haenszel analysis of variance statistic was used to compare groups on the stages-of-change variables. RESULTS: Beginning with the smoking ban and continuing for 5 years after implementation, statistically significant differences in the postban quit ratio were observed between employees of smoke-free hospitals who were smokers and counterparts in the community (P<.001). Despite preban differences in smoking intensity, the overall difference in postban quit ratios remained significant even after multivariate adjustment for socioeconomic, demographic, and smoking intensity variables. For those sites that were 5 years postban, the quit ratio was 0.506 in smoke-free workplaces compared with 0.377 in workplaces where smoking was permitted. In all but 1 category, the intervention group was further along the stages-of-change continuum toward quitting smoking than the comparison group (P<.001). CONCLUSION: American hospitals' experiences with smoking bans, which directly affect more than 5 million workers, should be examined by other industries as a method of improving employee health. Workplace smoking bans could also be effective in saving lives, reducing health care costs, addressing safety concerns, and decreasing operating and maintenance expenses of employers.

Smoking bans in US hospitals. Results of a national survey.

OBJECTIVE: To examine compliance and characteristics of hospitals with tobacco control standards enacted by the Joint Commission of Accreditation of Healthcare Organizations (JCAHO). DESIGN AND SETTING: On-site national survey of hospitals as part of routine JCAHO accreditation visits. PARTICIPANTS: A total of 3327 US hospitals received site visits in 1992 and 1993 and were matched with American Hospital Association Annual Survey of Hospitals data. MAIN OUTCOME MEASURES: Compliance or noncompliance with tobacco control standards; location in a tobacco-producing state; and organizational characteristics, including provision of psychiatric/alcohol-chemical dependency services. RESULTS: Two years after implementation, 95.6% of hospitals met the new JCAHO smoking ban standard; 90.9% of hospitals were in compliance with a second smoking standard requiring development and use of medical criteria for physician-ordered exceptions to the ban. Hospitals in tobacco-producing states had higher-than-average rates of compliance when compared with hospitals in other states. Hospitals providing psychiatric and/or substance abuse services had lower-than-average rates of compliance. CONCLUSION: This first industry-wide smoking ban has been successful. However, hospitals should consider evaluating the use of medical exceptions to this policy.