Serial testing for latent tuberculosis infection in transplant candidates: a retrospective review.

BACKGROUND: Accurately identifying latent tuberculosis (TB) infection (LTBI) in liver and renal transplant candidates is important because of the risks associated with both treatment of LTBI and reactivation of disease in this population. Many programs advocate yearly screening of patients awaiting organ transplantation. The reproducibility of serial interferon-gamma release assay (IGRA) testing in transplant candidates has not been studied. METHODS: We conducted a retrospective longitudinal study of patients listed for liver or kidney transplantation between January 1, 2005 and February 1, 2012 at the University of Illinois Medical Center at Chicago. Data collected included demographics, transplant type, IGRA results, treatment received, and mortality. RESULTS: The study population was comprised of 795 adults; 79 (10%) had at least 1 indeterminate result; indeterminate results were less common in men (P = 0.01) and more common in liver transplant candidates (P < 0.001). The reversion frequency was 27% with a rate of 158.1 reversions in 1000 person-years. A higher magnitude of initial TB response values was predictive of consistently positive results (P < 0.001). The conversion frequency was 15% with a rate of 82.6 conversions in 1000 person-years. Among those who converted, the values of the IGRA varied, with 48% having a TB response of <1 IU/mL, 41% 1-5 IU/mL, and only 10% >5 IU/mL. CONCLUSIONS: A significant number of conversions and reversions occur during serial IGRA testing of transplant candidates. Delineating true-positive converters from false-positives is an issue that warrants further study.

Current practices for treatment of respiratory syncytial virus and other non-influenza respiratory viruses in high-risk patient populations: a survey of institutions in the Midwestern Respiratory Virus Collaborative.

BACKGROUND: The optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non-influenza respiratory viruses in Midwestern transplant centers. METHODS: A survey assessing strategies for RSV and other non-influenza respiratory viral infections was sent to 13 centers. RESULTS: Multiplex polymerase chain reaction assay was used for diagnosis in 11/12 centers. Eight of 12 centers used inhaled ribavirin (RBV) in some patient populations. Barriers included cost, safety, lack of evidence, and inconvenience. Six of 12 used intravenous immunoglobulin (IVIG), mostly in combination with RBV. Inhaled RBV was used more than oral, and in the post-stem cell transplant population, patients with lower respiratory tract infection (LRTI), graft-versus-host disease, and more recent transplantation were treated at higher rates. Ten centers had experience with lung transplant patients; all used either oral or inhaled RBV for LRTI, 6/10 treated upper respiratory tract infection (URTI). No center treated non-lung solid organ transplant (SOT) recipients with URTI; 7/11 would use oral or inhaled RBV in the same group with LRTI. Patients with hematologic malignancy without hematopoietic stem cell transplantation were treated with RBV at a similar frequency to non-lung SOT recipients. Three of 12 centers, in severe cases, treated parainfluenza and metapneumovirus, and 1/12 treated coronavirus. CONCLUSIONS: Treatment of RSV in immunocompromised patients varied greatly. While most centers treat LRTI, treatment of URTI was variable. No consensus was found regarding the use of oral versus inhaled RBV, or the use of IVIG. The presence of such heterogeneity demonstrates the need for further studies defining optimal treatment of RSV in immunocompromised hosts.

Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes.

BACKGROUND: The standard treatment of latent tuberculosis infection (LTBI) is associated with toxicities and data are limited on tolerability among patients with advanced organ disease listed for transplant. Alternate options are available, but they have yet to be studied in this population. METHODS: A retrospective review of the treatment of LTBI among kidney and/or liver transplant candidates was conducted to assess factors impacting therapy initiation, tolerability, and completion of therapy. RESULTS: Of 174 eligible patients, treatment of LTBI was initiated in 129, of which 91 were listed for kidney transplant and 38 were listed for liver or liver/kidney transplant. Infectious Diseases consultation was independently associated with treatment initiation when controlling for waitlisted organ and receipt of hemodialysis (odds ratio [OR] 81.14, 95% confidence interval [CI] 23.94-274.94, P < 0.001). Documented completion of first-line therapy was 47% overall, and 49% and 39%, respectively, among kidney and liver/kidney candidates (P = not significant). On multivariable analysis, controlling for baseline aspartate aminotransferase and waitlisted organ, first-line receipt of rifampin was associated with lower rates of treatment completion (OR 0.19, 95% CI 0.05-0.77, P = 0.02). CONCLUSION: Based on medical record documentation, completion of first-line therapy was <50% in this cohort, although this is likely an underestimate, as 34% of patients had no chart documentation that therapy was completed. Approximately 20% of patients did not complete first-line therapy because of adverse effects.

A multicenter study of histoplasmosis and blastomycosis after solid organ transplantation.

AIM: A review of the clinical presentation, diagnosis, treatment and outcomes of 30 solid organ transplant recipients (SOTRs) with histoplasmosis or blastomycosis from 3 Midwestern academic medical centers. BACKGROUND: The endemic fungal pathogens, Histoplasma capsulatum and Blastomyces dermatitidis, may cause severe infection in SOTRs. In this report, we describe the clinical presentation, diagnosis, treatment, and outcomes of these endemic fungal infections (EFIs) among SOTRs at 3 academic transplant centers. METHODS: A retrospective review was conducted of SOTRs with histoplasmosis or blastomycosis from 3 Midwestern medical centers in the United States. Data collected included demographics, immunosuppression, clinical presentation, method of diagnosis, antifungal treatment, response to therapy, and patient and graft survival. RESULTS: Between 1996 and 2008, 30 transplant recipients with histoplasmosis or blastomycosis were identified, giving a cumulative incidence of infection of 0.50% (30/5989); 73% of the study patients were renal transplant recipients, and the median time to disease onset after transplantation was 10.5 months. The lungs were the most common site of infection (83%), and 60% had disseminated disease. Urine antigen testing was positive in all patients in whom it was performed (23/23). Initial antifungal therapy consisted of amphotericin B in 70%, and 87% received azoles, typically itraconazole (83%). Two patients developed relapsed infection and 7 patients had graft failure after EFI. Overall mortality was 30%, with an attributable mortality of 13%. CONCLUSIONS: As in several previous single-center studies, the incidence of post-transplant histoplasmosis and blastomycosis was <1%, but often resulted in disseminated infection. In this cohort, EFI was associated with a high rate of allograft loss and overall mortality.

Gastrointestinal tuberculosis in renal transplant recipients: case report and review of the literature.

Mycobacterium tuberculosis is an important opportunistic pathogen following renal transplantation and is often associated with adverse outcomes. Gastrointestinal tuberculosis (GITB) is an infrequent manifestation of TB but a potentially lethal one. We present a case of a renal allograft recipient with GITB 18 months after transplant and review other published cases to identify the typical presenting symptoms, risk factors, and natural history. Treatment of GITB is also discussed.

Limitations of current antiretroviral agents and opportunities for development.

Significant progress has been made in the field of human immunodeficiency virus (HIV) pharmacotherapy. This is a remarkable achievement given that the virus was first recognized in the United States in 1981 and the first antiretroviral (ARV) agent became available in 1987. There are now 20 medications in 4 different classes approved by the Food and Drug Administration (FDA) for the treatment of HIV and the carefully orchestrated use of these agents has dramatically decreased HIV mortality. However, the currently available agents have concerning limitations. These include potentially life-threatening side effects, drug interactions, loss of effectiveness over time due to resistance and the need for an extremely high level of medication adherence to achieve viral suppression. In the following review, important features of the presently available agents are described, and the characteristics of an ideal ARV agent defined.

Anti-capsular antibodies activate killing of Escherichia coli O8:K87 by the alternate complement pathway in porcine serum.

Enterotoxigenic Escherichia coli (ETEC) strains that produce K88 (F4)+ fimbria are important causes of diarrhea and post-diarrheal septicemia in swine. ETEC O8:K87, a serotype represented by a number of these strains, is typically serum resistant. Strain-specific antibodies are known to activate alternative C pathway-mediated killing of other serum-resistant E. coli [Hill, A.W., Shears, A.L., Hibbitt, K.G., 1978. The requirement of specific antibody for the killing of E. coli by the alternate complement pathway in bovine serum. Immunology 34, 131-136], but their antigenic targets have not been determined. We tested the hypothesis that anti-K87 antibodies activate alternative pathway-mediated killing of ETEC O8:K87. Pigs were immunized with ETEC O8:K87 strain 2534-86 cells or purified K87 polysaccharide. Post-, but not pre-immunization sera killed 2534-86 cells, and absorption with 2534-86 cells or by K87 affinity chromatography eliminated bactericidal activity. Complementation of absorbed serum with anti-K87 antibodies restored bactericidal activity, confirming the ability of these antibodies to activate C-mediated serum killing. Serum from age-matched, non-vaccinated control pigs also killed 2534-86. This activity was eliminated by absorption with 2534-86 cells, but not K87 affinity chromatography, indicating that specific non-capsular antibodies are also able to activate C-mediated killing. In all cases, Mg-EGTA-treated serum was as effective as non-treated serum in killing, suggesting that bactericidal activity was mediated predominantly if not exclusively via the alternative C pathway.

Risk factors for wound healing complications in sirolimus-treated renal transplant recipients.

Impaired surgical site healing occurs in 20% to 50% of sirolimus (SRL)-treated renal transplant (RT) recipients, with most patients having received concomitant corticosteroids. We determined the incidence of surgical site complications among RT recipients receiving SRL with mycophenolate mofetil (MMF), with most patients on a steroid-avoidance protocol. SRL/MMF patients with complications within 3 months of transplantation were compared with 1) SRL/MMF patients without them and 2) matched RT recipients receiving tacrolimus (FK)/MMF. Between January 2002 and March 2005, 44 of 300 (15%) RT recipients received SRL within 6 weeks of transplantation. Fourteen (31.8%) developed lymphocele, bladder leak, wound dehiscence, cellulitis, or an abscess. Obesity (BMI > or =30 kg/m2) was significantly associated with problems: the mean BMI of SRL cases with complications was 29.9 kg/m2 vs 25.4 kg/m2 for SRL patients without them (P = .047). Seventy-one percent of obese SRL patients experienced complications compared with 24.3% (P = .025) of non-obese SRL patients. Surgical treatment was required in 29% of patients. Rates of maintenance steroid use were similar in SRL complicated cases compared with SRL patients without them. The FK control group showed a lower rate of complications (14.3%; P = .163) despite similar BMI, rejection rates, and chronic steroid use as the SRL group. Obesity and graft rejection were independent predictors of complications. Thus, among a group of predominantly steroid-free recipients on SRL, the rates of wound complications were similar to those seen previously, but the highest risk for them was observed in obese recipients and in those with acute rejection episodes. Wound complications were associated with significant morbidity.

Childhood asthma.

Asthma prevalence in children has increased 58% since 1980. Mortality has increased by 78%. The burden of the disease is most acute in urban areas and racial/ethnic minority populations. Hospitalization and morbidity rates for nonwhites are more than twice those for whites. Asthma is characterized by recurrent wheezing, breathlessness, chest tightness, and coughing. Research in the past decade has revealed the importance of inflammation of the airways in asthma and clinical treatment to reduce chronic inflammation. Asthma is associated with production of IgE to common environmental allergens including house dust mite, animal dander, cockroach, fungal spores, and pollens. Some interventions to reduce symptoms through control of dust mite and animal dander have had positive results. Control of symptoms through interventions to reduce exposures to cockroach antigen has not been reported. Studies illustrating causal effects between outdoor air pollution and asthma prevalence are scant. Increases in asthma prevalence have occurred at the same time as general improvements in air quality. However, air quality appears to exacerbate symptoms in the child who already has the disease. Decreased pulmonary function has been associated with exposure to particulates and bronchial hyperresponsiveness to smoke, SO(2) and NO(2). Symptoms have been correlated with increased levels of respirable particulates, ozone, and SO(2). Interventions that reduce the negative outcomes in asthma associated with outdoor environmental factors have not been reported. Control of asthma in children will entail the collaborative efforts of patients, family, clinical professionals, and school personnel, as well as community-wide environmental control measures and conducive national and local policies based on sound research.

The Guide to Community Preventive Services will be influential in academic health centers: education, research and links with practice.

PIP: In both clinical medicine and in public health, programs, services and advice have been built based on individual judgments or professional consensus. There has been a lack of educational commitment, a knowledge base and a practice ethic solidly grounded in research and evaluation. The introduction of the Guide to Community Preventive Services, which has a clear link with the categories of immunizations, counseling services and screening tests, is considered to be influential in academic health centers who are engaged in research and evaluation studies. In addition, principles and guidelines for community-based research will facilitate real-world tests of ideas and guidelines for community preventive services. Performance standards and cost-effectiveness analyses will be expected by all payers and by policy-makers. Moreover, scientific advances, especially in the emerging field of public health genetics, will be incorporated. Thus, academics, practitioners, and employers should join forces to persuade payers to accept evidence-based convergence of related clinical guidelines. Such initiatives will improve the chances for increased investment in preventive medicine and public health.^ieng

Impact of self-management education on the functional health status of older adults with heart disease.

This paper presents findings from the evaluation of a self-management education program based on self-regulation principles. Older men and women (N = 324) were randomly assigned to program and control groups. Outcomes were measured using the Sickness Impact Profile. Twelve months following baseline data collection, psychosocial functioning of program participants was significantly better than that of controls. Different program effects were noted when results were analyzed by participant gender.

Educational interventions for asthma in children.

BACKGROUND: Self-management education programs have been developed for children with asthma, but it is unclear whether such programs improve outcomes. OBJECTIVES: To determine the efficacy of asthma self-management education on health outcomes in children. SEARCH STRATEGY: Systematic search of the Cochrane Airways Group's and Cochrane Schizophrenia Group's Special Registers of Controlled Trials and hand searches of the reference lists of relevant review articles. SELECTION CRITERIA: Randomized and controlled clinical trials of asthma self-management education programs in children and adolescents aged 2 -18 years. DATA COLLECTION AND ANALYSIS: All studies were assessed independently by two reviewers. Disagreements were settled by consensus. Study authors were contacted for missing data or to verify methods. Subgroup analyses examined the impact of type and intensity of educational intervention, self-management strategy, trial type, asthma severity, adequacy of follow-up, and study quality. MAIN RESULTS: Of 45 trials identified, 32 studies involving 3706 patients were eligible. Asthma education programs were associated with moderate improvement in measures of airflow (standardized mean difference [SMD] 0.50, 95% confidence interval [CI] 0.25 to 0.75) and self-efficacy scales (SMD 0.36, 95% CI 0.15 to 0.57). Education programs were associated with modest reductions in days of school absence (SMD -0.14, 95% CI -0.23 to -0.04), days of restricted activity (SMD -0.29, 95% CI -0.49 to -0.08), and emergency room visits (SMD -0.21, 95% CI -0.33 to -0.09). There was a reduction in nights disturbed by asthma when pooled using a fixed-effects but not a random-effects model. Effects of education were greater for most outcomes in moderate-severe, compared with mild-moderate asthma, and among studies employing peak flow versus symptom-based strategies. Effects were evident within the first 6 months, but for measures of morbidity and health care utilization, were more evident by 12 months. REVIEWER'S CONCLUSIONS: Asthma self-management education programs in children improve a wide range of measures of outcome. Self-management education directed to prevention and management of attacks should be be incorporated into routine asthma care. Conclusions about the relative effectiveness of the various components are limited by the lack of direct comparisons. Future trials of asthma education programs should focus on morbidity and functional status outcomes, including quality of life, and involve direct comparisons of the various components of interventions.

Self-management of asthma by adult patients.

Review of eighteen adult self-management education program evaluations comprising clinical trials showed significant achievement in five categories of outcome: (1) asthma knowledge; (2) patient perceptions and psychological status; (3) behavior related to medicine use, delivery devices and environmental triggers; (4) functioning and control of symptoms; and (5) health care use. Not every program achieved in all of these categories, probably because interventions of adequate power to elicit change in one category of outcome were not powerful enough to realize change in another category. An alternative explanation may be that in some studies assessment measures were inadequate. Asthma management by patients is influenced by their social environment and this aspect of control is least well understood. A small qualitative study suggested themes among adult patients that describe intra- and interpersonal factors enabling or hindering self-management including: the ability to acquire information; self-regulation; relations with family, friends and coworkers; and, relationships with clinicians. Research is needed that provides greater understanding of social environments in asthma management, produces standardized measurement tools, and tests more robust and theory-based interventions.

Self-management of the health care regimen: a comparison of nurses' and cardiac patients' perceptions.

This study compared perceptions of 129 elderly cardiac patients regarding their health status and self-management skills with corresponding assessments by outpatient nursing staff members. Nurse-patient perceptions were most congruent on general questions regarding the heart condition. Differences were most apparent regarding how aware patients were of being asked to follow a regimen for managing their heart problems; what specific components comprised the regimens the patients were to follow; and how much confidence patients had in their ability to comply with specific components of the regimen. Congruence in perceptions of nurses and patients varied by the sex of the patient. Findings suggest that careful and continuous assessment of patients' perceptions about their condition and ongoing instruction regarding specifics of the therapeutic regimen are key elements in efforts to enhance elderly patients' self-management skills.

Communication within low income families and the management of asthma.

This study examines the effects of communication between low income urban parents and children about a chronic disease on the extent to which parent and child effectively manage the illness. Four asthma communication factors were identified by principal component analysis. We found that mothers whose preferred language was Spanish, and families who were not receiving public assistance, communicated more frequently about asthma in general. Spanish speaking mothers and their children communicated more about potential home treatments for asthma, and the more adults in the household the less there was communication about the need for emergency services for asthma. Mothers who preferred to speak Spanish had higher levels of management of the most recent asthma attack. Those whose children communicated with them about asthma in general were higher level managers. Children who influenced their parents' decisions about school attendance, and those whose mothers were more highly educated, had higher levels of asthma attack management. More educated mothers, ones whose children were younger at the time of the onset of asthma, and one who received public assistance, were more involved "in general" in their child's asthma care.

Increasing asthma knowledge and changing home environments for Latino families with asthmatic children.

We tested an asthma education program in 204 underserved Latino families with an asthmatic child. The education program consisted of one or two sessions delivered in each family's home in the targeted participant's preferred language by a bilingual, bicultural educator. We encouraged, but did not require, attendance by the child. The curriculum was culturally-tailored, and all participants received education on understanding asthma, preventing asthma attacks, and managing asthma. Outcomes included change in asthma knowledge and change in home environment asthma management procedures. Asthma knowledge increased significantly (39 to 50% correct from pre- to post-test, P < 0.001) and participants made significant changes to the child's bedroom environment (mean number of triggers decreased from 2.4 to 1.8, P < 0.001; mean number of controllers increased from 0.7 to 0.9, P < 0.001). The results support the value of asthma education and its importance in the national agenda to reduce health disparities among minorities.

Managing better: children, parents, and asthma.

To evaluate a health education program to improve family management of asthma, 310 children with asthma and their 290 parents were randomly assigned to a program or control group. Program families participated in health education designed to resolve specific management problems and build self-confidence in the ability to manage asthma. Following education, program parents scored better on an asthma self-management index than parents in the control group (+1.57 versus -0.83, P less than 0.0001). Program parents also scored better on two subindices of the self-management index: attack management (+0.87 vs. +0.42, P less than 0.05) and preventive measures (+0.42 vs. -0.35, P less than 0.05). Also, program parents reported significantly more use of guidelines to determine appropriate levels of physical activity for children. Following education, program children reported more use of three management steps than control children: productive cough or postural drainage (59% vs. 35%, P less than 0.004), breathing and relaxation exercises (80% vs. 65%, P less than 0.05), and attempts to stay calm (12% vs. 2%, P less than 0.05). Program children reported significantly less worry than control children about the limitations asthma imposes and about making mistakes at school.

Exploring self-efficacy as a predictor of disease management.

Self-efficacy is posited in social cognitive theory as fundamental to behavior change. Few health behavior studies have examined self-efficacy prospectively, viewed it as part of a reciprocal behavioral process, or compared self-efficacy beliefs in the same population across different behaviors. This article first discusses self-efficacy in its theoretical context and reviews the available prospective studies. Second, it explores self-efficacy as a predictor of disease management behaviors in 570 older women with heart disease. Although the R2 statistics in each case were modest, the construct is shown to be a statistically significant (p<.05) predictor at both 4 and 12 months postbaseline of several disease management behaviors: using medicine as prescribed, getting adequate exercise, managing stress, and following a recommended diet. Building self-efficacy is likely a reasonable starting point for interventions aiming to enhance heart disease management behaviors of mature female patients.