Thomas P. Monson

Pathogenic Aspergillus Species Recovered from a Hospital Water System: A 3-Year Prospective Study

Nosocomial aspergillosis, a life-threatening infection in immunocompromised patients, is thought to be caused primarily by Aspergillus organisms in the air. A 3-year prospective study of the air, environmental surfaces, and water distribution system of a hospital in which there were known cases of aspergillosis was conducted to determine other possible sources of infection. Aspergillus species were found in the hospital water system. Significantly higher concentrations of airborne aspergillus propagules were found in bathrooms, where water use was highest (2.95 colony-forming units [cfu]/m(3)) than in patient rooms (0.78 cfu/m(3); P=.05) and in hallways (0.61 cfu/m(3); P=.03). A correlation was found between the rank orders of Aspergillus species recovered from hospital water and air. Water from tanks yielded higher counts of colony-forming units than did municipal water. An isolate of Aspergillus fumigatus recovered from a patient with aspergillosis was genotypically identical to an isolate recovered from the shower wall in the patients room. In addition to the air, hospital water systems may be a source of nosocomial aspergillosis.

Infections with Ehrlichia chaffeensis and Ehrlichia ewingii in Persons Coinfected with Human Immunodeficiency Virus

The clinical course and laboratory evaluation of 21 patients coinfected with human immunodeficiency virus (HIV) and Ehrlichia chaffeensis or Ehrlichia ewingii are reviewed and summarized, including 13 cases of ehrlichiosis caused by E. chaffeensis, 4 caused by E. ewingii, and 4 caused by either E. chaffeensis or E. ewingii. Twenty patients were male, and the median CD4(+) T lymphocyte count was 137 cells/microL. Exposures to infecting ticks were linked to recreational pursuits, occupations, and peridomestic activities. For 8 patients, a diagnosis of ehrlichiosis was not considered until > or =4 days after presentation. Severe manifestations occurred more frequently among patients infected with E. chaffeensis than they did among patients infected with E. ewingii, and all 6 deaths were caused by E. chaffeensis. Ehrlichiosis may be a life-threatening illness in HIV-infected persons, and the influence of multiple factors, including recent changes in the epidemiology and medical management of HIV infection, may increase the frequency with which ehrlichioses occur in this patient cohort.

Use of Long-Acting Tetracyclines for Methicillin-Resistant Staphylococcus aureus Infections: Case Series and Review of the Literature

BACKGROUND Few data exist on the efficacy of the long-acting tetracyclines doxycycline and minocycline against methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS The medical records of 24 patients with serious tetracycline-susceptible MRSA infections who were treated with doxycycline or minocycline were reviewed. A review of the literature on the use of these antibiotics for treatment of both methicillin-susceptible and methicillin-resistant S. aureus infection was also performed. RESULTS Complicated skin and skin-structure infections were most common (67%). Clinical cure was achieved in 20 (83%) of 24 patients in our case series. Both drugs were well-tolerated. The review of the literature on a total of 85 patients with S. aureus infection revealed similar results. CONCLUSIONS Long-acting tetracyclines may be a reasonable treatment alternative for patients with certain types of MRSA infection.

Linezolid-Induced Pure Red Blood Cell Aplasia

We report a case of reversible pure red blood cell aplasia that developed in a patient who had received 8 weeks of linezolid therapy.

Development and implementation of collaborative care for depression in HIV clinics

We sought to develop and implement collaborative depression care in human immunodeficiency virus (HIV) clinics in a project called HIV Translating Initiatives for Depression into Effective Solutions (HITIDES). Here we describe: (i) the formative evaluation (FE) conducted prior to implementation; (ii) the process used to adapt the primary care collaborative care model for depression to specialty HIV clinics; and (iii) the intervention itself. The overall design of HITIDES was a multi-site randomized trial in United States Department of Veterans Affairs (VA) HIV clinics comparing the depression collaborative care intervention to usual depression care. Qualitative methods were used for the FEs and informed the evidence-based quality improvement (EBQI) methods that were used for adapting and implementing the intervention. Baseline assessments were completed by 249 depressed HIV participants. Summaries of respective key informant interviews with eight HIV patients who were receiving depression treatment and 25 HIV or mental health (MH) providers were presented to each site. EBQI methods were used to tailor the HITIDES intervention to each site while maintaining true to the evidence base for depression collaborative care. EBQI methods provided a useful framework for intervention adaptation and implementation. The HITIDES study provides the opportunity to evaluate collaborative depression care in a specialty physical health clinic setting with a population that has a high prevalence of depression and MH comorbidity.

Tumor-Targeted Cell Killing with 8-Hydroxyquinolyl-Glucuronide

Many tumors show elevated levels of hydrolytic enzymes that may be associated with invasive processes. The RIF-1 murine tumor has levels of beta-glucuronidase that are more than four times higher than those in liver. Elevated tumor glucuronidase levels can be used as a basis for tumor-targeted therapy when systemically administered glucuronides of cytotoxic drugs are deconjugated preferentially at the tumor site. In this study we have used 8-hydroxyquinoline (8-OHQ) as a model compound for such a tumor-targeting concept. We showed that RIF tumors and spleen had the highest beta-glucuronidase activity in C3H mice; for example, RIF tumors released approximately seven times more phenolphthalein per gram of tissue from its glucuronide than liver, when compared under identical conditions. In vitro, low concentrations of 8-OHQ that might be achievable in vivo, ranging from 1 to 10 microM reduced cell survival by four orders of magnitude, while 1 mM 8-hydroxyquinolyl-glucuronide (1 h, 37 degrees C) resulted in only modest (S = 54%) cytotoxicity. Combination treatments of 8-OHQ (2.5 or 5 microM) with either hyperthermia or X radiation did not significantly change the slope of survival curves for RIF tumors in vitro, but suggest that targeted 8-OHQ toxicity combined with local hyperthermia and/or irradiation may be useful for significantly increasing therapeutic gains in vivo.

Tumor-targeted delivery of 8-hydroxyquinoline

RIF-1 mouse tumors express high levels of beta-glucuronidase activity relative to most normal tissues. The high activity can be exploited for targeting specific drugs preferentially to tumor tissues. In this study we examined the kinetics of 8-hydroxyquinoline (8-OHQ) accumulation in tumor and in several normal tissues resulting from the in vivo deconjugation of 8-hydroxyquinolyl-glucuronide (8-OHQ-GlcA). Tumors were acidified with D-glucose and NaHCO3 prior to the administration of 8-OHQ-GlcA; subsequently the deconjugated aglycone, 8-OHQ, accumulated preferentially in tumors and reached peak levels between 30 and 60 min after the 8-OHQ-GlcA injection. Mild hyperthermia of 30 min at 43 degrees C to the tumors further increased their peak 8-OHQ levels by a factor of 2-3. Some normal tissues, mostly kidney, liver, and colon, also accumulated 8-OHQ, but the aglycone appeared early in the normal tissues (near 30 min post-injection) and was significantly reduced by 60 min when 8-OHQ remained high in the tumor. Administration of 8-OHQ-GlcA alone, without prior tumor acidification, failed to produce measurable accumulations of 8-OHQ in tumors and in normal tissues. Tissue clearance of 8-OHQ is mediated primarily by the enzymatic reconjugation of 8-OHQ via UDP-glucuronosyltransferase (UDPGT). UDPGT activity was high in liver, kidney, and bowel, but low in the RIF tumor, spleen, muscle, and brain. Hyperthermia had only a modest effects on UDPGT activity: a heat dose of 30 min at 45 degrees C reduced activity less than 60%. Thus, preferential accumulation and prolonged retention of 8-OHQ in RIF tumors may be caused by a combination of factors: a) high tumor beta-glucuronidase activity, b) selective tumor acidification during hyperglycemia, c) low tumor UDPGT activity, and d) other factors, such as tumor blood flow.

Exposure to Pretreatment Hypothermia as a Determinant of Heat Killing

When Chinese hamster ovary (CHO) cells were exposed to 22 degrees C for 2 hr prior to 42.4 degrees C hyperthermia, neither the shoulder region of the survival curve nor the characteristic development of thermotolerance after 3-4 hr of heating were observed. Absolute cell survival after 4 hr at 42.4 degrees C was decreased by a factor of between 10 and 100 (depending on the rate of heating of nonprecooled controls). Conditioning at 30 degrees C for 2 hr, 26 degrees C for 2 hr, or 22 degrees C for 20 min followed by heating to 42.4 degrees C over 30 min did not result in sensitization. Prolonged (16 hr) conditioning at 30 degrees C, however, increased the cytotoxicity of immediate exposure to 41.4 or 45 degrees C with maximum sensitization to 45 degrees C occurring after 6 hr at 30 degrees C. Both 3- and 18-hr pretreatments at 30 degrees C similarly increased the cytotoxicity of 45-41.5 degrees C step-down heating (D0 = 28 min in precooled versus 40 min in nonprecooled cells).

HIV patient and provider feedback on a telehealth collaborative care for depression intervention

ABSTRACT In the HIV Translating Initiatives for Depression into Effective Solutions project, we conducted a randomized controlled effectiveness and implementation trial comparing depression collaborative care with enhanced usual care in Veterans Health Administration HIV clinics in the US. An offsite HIV depression care team including a psychiatrist, a depression care manager (DCM), and a clinical pharmacist provided collaborative care using a stepped-care model of treatment and made recommendations to providers through the electronic health record system. The DCM delivered care management to HIV patients through phone calls, performing routine assessments and providing counseling in self-management and problem-solving. The DCM documented all calls in each patient’s electronic medical record. In this paper we present results from interviews conducted with patients and clinical staff in a multi-stage formative evaluation (FE). We conducted semi-structured FE interviews with 26 HIV patients and 30 clinical staff at the three participating sites during and after the trial period to gather their experiences and perspectives concerning the intervention components. Interviews were transcribed verbatim and analyzed using rapid content analysis techniques. Patients reported high satisfaction with the depression care manager (DCM) phone calls. Both HIV and mental health providers reported that the DCM’s chart notes in the electronic health record were very helpful, and most felt that a dedicated DCM for HIV patients is ideal to meet patient needs. Sites encountered barriers to achieving and maintaining universal depression screening, but had greater success when such screening was incorporated into routine intake processes. FE results demonstrated that depression care management via telehealth from an offsite team is acceptable and helpful to both HIV patients and their providers. Given that a centralized offsite depression care team can deliver effective, cost-effective, cost-saving services for multiple HIV clinics in different locations with high patient and provider satisfaction, broad implementation should be considered.

Cost-Effectiveness of Collaborative Care for Depression in HIV Clinics.

Objective:To examine the cost-effectiveness of the HIV Translating Initiatives for Depression Into Effective Solutions (HITIDES) intervention. Design:Randomized controlled effectiveness and implementation trial comparing depression collaborative care with enhanced usual care. Setting:Three Veterans Health Administration HIV clinics in the Southern United States. Subjects:Two hundred forty-nine HIV-infected patients completed the baseline interview; 123 were randomized to the intervention and 126 to usual care. Intervention:HITIDES consisted of an offsite HIV depression care team that delivered up to 12 months of collaborative care. The intervention used a stepped-care model for depression treatment, and specific recommendations were based on the Texas Medication Algorithm Project and the VA/Department of Defense Depression Treatment Guidelines. Main Outcome Measures:Quality-adjusted life years (QALYs) were calculated using the 12-Item Short Form Health Survey, the Quality of Well Being Scale, and by converting depression-free days to QALYs. The base case analysis used outpatient, pharmacy, patient, and intervention costs. Cost-effectiveness was calculated using incremental cost-effectiveness ratios (ICERs) and net health benefit. ICER distributions were generated using nonparametric bootstrap with replacement sampling. Results:The HITIDES intervention was more effective and cost saving compared with usual care in 78% of bootstrapped samples. The intervention net health benefit was positive and therefore deemed cost-effective using an ICER threshold of