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Biomedical subjects

Donald E Craven

Publications and source records attributed to Donald E Craven.

At least 19 recordsLinked to original sources

Endothelial function in HIV-infected persons.

BACKGROUND: Several reports have suggested an increased risk of coronary disease in human immunodeficiency virus (HIV)-infected patients receiving protease inhibitors (PIs). Impaired endothelium-dependent vasodilation is a putative surrogate marker of coronary atherosclerotic disease. METHODS: The present study evaluated the effect of HIV infection and antiretroviral treatment on endothelial vasomotor function, by assessing brachial artery flow-mediated dilation (FMD). A total of 75 HIV-infected patients were compared with 223 control subjects who were presumed to be HIV uninfected. RESULTS: HIV-infected patients had significantly impaired FMD, compared with control subjects (mean +/- SD, 7.3% +/- 4.4% vs. 11.1% +/- 6.3%; P < .0001). When adjustments were made for smoking status, sex, and body mass index, the difference between the 2 groups remained statistically significant (P < .01). In a cross-sectional analysis of the HIV-infected patients, we found significant associations between FMD and current injection drug use, hazardous drinking, HIV load, and alpha-high-density lipoprotein triglyceride levels, but not PI therapy. In a multivariate analysis, only current injection drug use and a lower alpha-high-density lipoprotein triglyceride level were significantly associated with FMD. CONCLUSIONS: HIV-infected patients have significant impairment of endothelial function, and this impairment is worse among those with elevated levels of HIV replication, particularly injection drug users.

Adult↗

What is healthcare-associated pneumonia, and how should it be treated?

PURPOSE OF REVIEW: In contrast to patients at risk for hospital-acquired pneumonia or mechanically ventilated patients at risk for ventilator-associated pneumonia, healthcare-associated pneumonia is a relatively new clinical entity that includes a spectrum of adult patients who have close association with acute care hospitals or reside in chronic care settings that increase their risk for pneumonia caused by multi-drug-resistant bacteria. Multi-drug-resistant pathogens include methicillin-resistant Staphylococcus aureus and Gram-negative bacilli, such as Pseudomonas aeruginosa, extended-spectrum beta-lactamase-producing Klebsiella pneumoniae, and Acinetobacter species. New guidelines for the management and prevention of hospital-acquired pneumonia, ventilator-associated pneumonia and healthcare-associated pneumonia from the American Thoracic Society and the Infectious Diseases Society of America were published in 2005 and are highlighted in this article. RECENT FINDINGS: Recent data indicate that types of multi-drug-resistant pathogens may vary in different healthcare settings, and that individuals infected with multi-drug-resistant pathogens are more likely to receive inappropriate initial antibiotic therapy, which may result in poorer outcomes in terms of patient morbidity, mortality and increased length of hospital stay. SUMMARY: This review highlights key points in the new recommendations and principles for initiating, de-escalating and stopping antibiotic therapy in individuals with healthcare-associated pneumonia. Widespread implementation of these guidelines is needed in healthcare institutions in order to reduce patient morbidity, mortality, and healthcare costs.

Anti-Bacterial Agents↗

Fusarium oxysporum pneumonia in an immunocompetent host.

A case of symptomatic pulmonary infection caused by Fusarium oxysporum occurred in a woman after she had cleaned out bird droppings from a boat house. She was also a gardener who had mild, chronic obstructive lung disease, but who had no evidence of systemic immunosuppression. She was treated with oral voriconazole for four months and had marked clinical improvement and mycological cure. To the best of our knowledge, this is the first reported case of isolated pulmonary fusariosis in an apparently immunocompetent person. Oral voriconazole therapy was effective in this clinical setting.

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Preventing ventilator-associated pneumonia in adults: sowing seeds of change.

Ventilator-associated pneumonia (VAP), a major cause of ICU infection, results in high morbidity, mortality, and health-care costs. Multiple risk factors for VAP involve complex host factors and ubiquitous pathogens that require several different types of prevention strategies. Prevention efforts should focus on reducing bacterial colonization, and limiting aspiration, antibiotic exposure, and use of invasive devices. Although evidence-based prevention guidelines are available, they are lengthy, often ignored, and not implemented. New insights into the barriers to implementation of effective prevention programs are emerging. This article provides highlights from recent guidelines and publications discussing VAP prevention strategies and examines barriers to their implementation. Prevention and implementation of cost-effective strategies to reduce risk and improve patient outcomes should be prioritized. Clearly, prevention programs should be population specific and may vary among hospitals, but a multidisciplinary prevention team led by a "champion" is recommended to help set priorities, benchmarking goals, analyze data, and sow the seeds of change for risk reduction.

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HIV infection does not affect the performance of noninvasive markers of fibrosis for the diagnosis of hepatitis C virus-related liver disease.

BACKGROUND: Noninvasive markers of hepatic fibrosis hold great promise to stage liver fibrosis and to monitor disease progression. To date, few studies have assessed the performance of the currently available markers of hepatic fibrosis in HIV-infected cohorts. The aim of the current study was to compare the diagnostic performance and characteristics of a number of noninvasive markers of hepatic fibrosis in populations of hepatitis C virus (HCV)-infected patients with and without HIV infection. METHODS: A sample of 97 subjects (40 HCV/HIV-coinfected, 57 HCV-infected) undergoing liver biopsy as part of an ongoing prospective cohort study was evaluated. Liver biopsies were assessed by a single hepatopathologist and scored according to Ishak criteria. Noninvasive markers of fibrosis studied included international normalized ratio, platelet count, aspartate aminotransferase (AST)/alanine aminotransferase ratio, AST platelet ratio index (APRI), Forns index, procollagen III N peptide, hyaluronic acid, and YKL-40. RESULTS: The correlations between fibrosis markers with the stage of fibrosis and the diagnostic performance of each of the tests were similar in the groups with and without HIV infection. Although a trend to improved diagnostic performance in the HCV/HIV-coinfected group was observed, this may be related to the small sample size. CONCLUSIONS: The diagnostic performance of the evaluated noninvasive markers of liver fibrosis is equivalent in HCV/HIV-coinfected and HCV-infected subjects. These tests may be of value for the clinical evaluation of HCV/HIV-coinfected patients and warrant further study.

Adult↗

Health-related quality of life of patients with HIV disease: impact of hepatitis C coinfection.

Health-related quality of life (HRQOL) is diminished in patients infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV), but the effect of HIV/HCV coinfection on HRQOL is unknown. We compared the HRQOL of urban HIV/HCV coinfected patients with that of patients infected with either HCV or HIV alone. We then compared the 3 groups with a US population sample, adjusting for demographic characteristics. HRQOL for the group of HIV/HCV coinfected patients was statistically similar to that of HRQOL in patients with either HCV or HIV alone, but the 3 groups had a significantly decreased HRQOL than did the adjusted US population. Using multivariate techniques, we determined that age, unemployment, injection drug use, and depression were associated with impaired HRQOL. These findings underscore the importance of a multidisciplinary approach to the treatment of these patient populations.

Adult↗

Healthcare-associated pneumonia in adults: management principles to improve outcomes.

Guidelines for Management of HAP were developed jointly by the ATS and IDSA in 2004. These guidelines were designed to improve patient outcomes and to decrease the emergence of MDR pathogens (see Fig. 1).Principles include early initiation of appropriate and adequate antibiotic therapy after cultures of blood and sputum are obtained. Quantitative distal airway sampling by bronchoscopy provides greater diagnostic specificity for VAP: in one randomized study, improved outcomes were noted, compared with clinical diagnosis with qualitative endotracheal aspirates. Higher doses of initial, empiric antibiotics also are recommended. Assessment of the patient's clinical response to empiric antibiotics should be correlated with microbiologic results to streamline, de-escalate, or stop unnecessary anti-biotic treatment. Duration of therapy for uncomplicated HAP should be limited to 7 days followed by close monitoring for relapse after cessation of antibiotics. The authors suggest that prevention strategies target modifiable short- and long-term risk factors. They also advocate the use of a multidisciplinary team that is dedicated to the treatment and prevention of HCAP and the basic principle of the modern Hippocratic Oath: "I will prevent disease whenever I can, for prevention is preferable to cure."

Adult↗

Drug-selected resistance mutations and non-B subtypes in antiretroviral-naive adults with established human immunodeficiency virus infection.

The prevalence of human immunodeficiency virus (HIV) type 1 antiretroviral resistance is expected to be higher in recently infected antiretroviral-naive individuals than in those who have been infected longer. Antiretroviral-naive HIV-1-infected adults who presented to an outpatient clinic in an urban hospital in Boston for initial evaluation in 1999 were screened for drug-selected resistance mutations and phylogenetic subtype. Drug-selected mutations were identified in 16 (18%) of 88 subjects. Twelve (14%) included mutations associated with nucleoside reverse-transcriptase inhibitors, 4 (5%) included mutations associated with nonnucleoside reverse-transcriptase inhibitors, and 3 (3%) included mutations associated with protease inhibitors. Two (2%) had resistance mutations associated with multiple classes of drugs. Nine (10%) subjects had infection with non-B subtype HIV-1 and did not have drug-selected mutations. Serological results indicated infection for >/=6 months. Drug-selected mutations or non-B subtypes were detected in a substantial portion of antiretroviral-naive adults who had been infected for at least 6 months.

Adult↗

Invasive pulmonary aspergillosis soon after therapy with infliximab, a tumor necrosis factor-alpha-neutralizing antibody: a possible healthcare-associated case?

BACKGROUND: Infliximab is a chimeric monoclonal antibody against tumor necrosis factor (TNF)-alpha, used for the treatment of Crohn's disease and rheumatoid arthritis. Recently, an increased risk of infection due to Mycobacterium tuberculosis and rare cases of invasive fungal disease have been reported following infliximab therapy. CASE REPORT: A 73-year-old woman with chronic rheumatoid arthritis who had been treated with methotrexate, leflunomide, and prednisone was given the first of three doses of infliximab in June 2001. In July 2001, she presented with cough, and in August, she had a right upper lobe infiltrate that was treated with levofloxacin without improvement. In October, the patient had right upper and middle lobe infiltrates on a chest X-ray and computed tomography scan. At bronchoscopy, an endobronchial mass was biopsied, which demonstrated Aspergills fumigatus. Our patient had frequently accompanied her daughter on visits to another medical center following a stem cell transplant, where her daughter was instructed to wear a mask during all visits because of extensive building construction. We postulate that our patient may have acquired pulmonary aspergillosis during this period. Literature reviews on granulomatous diseases following infliximab therapy and hospital-acquired aspergillosis are presented. CONCLUSION: The temporal relationship between the administration of infliximab and A. fumigatus infection in this patient suggests a causal relationship and possible healthcare-associated acquisition. These data underscore the importance of both patient and family education on prevention strategies when potent immune-modulating medications such as infliximab have been prescribed.

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Cutaneous mucormycosis secondary to acquired reactive perforating collagenosis.

Acquired reactive perforating collagenosis (ARPC) is a rare perforating disease of the skin. It is characterized by hyperkeratotic papules with transepidermal elimination of degenerated material including collagen and elastic fibers. The disease presents clinically as umbilicated papules with a central adherent keratotic plug. Mucormycosis infection, caused by the molds of the class Zygomycetes and order Mucorales, generally occurs as an opportunistic infection. It presents most frequently in patients with diabetes mellitus, in patients with leukemia receiving chemotherapy, and in those on sustained immunosuppressive therapy. We describe a patient with type 2 diabetes mellitus and end-stage renal disease requiring hemodialysis in whom extensive cutaneous mucormycosis with secondary spread to the brain, lumbar spine, and breast developed in the setting of ARPC. To our knowledge, this is the first case report of a patient with ARPC who developed extensive cutaneous mucormycosis.

Collagen Diseases↗

Hepatitis C virus and human immunodeficiency virus coinfection in an urban population: low eligibility for interferon treatment.

One hundred eighty human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-coinfected patients were prospectively evaluated for suitability for interferon and ribavirin therapy. Of the 149 patients with chronic HCV infection who completed the evaluation, 44 (30%) were eligible for treatment and 105 (70%) were ineligible, with the main barriers being missed clinic visits, active psychiatric illness, active drug or alcohol use, decompensated liver disease, or medical illness.

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