Knowledge and practices regarding tuberculosis: a survey of final-year medical students from Canada, India and Uganda

CONTEXT: Tuberculosis is one of the most common infectious diseases worldwide and is responsible for the largest number of deaths from a single infectious cause. OBJECTIVE: The objective of this study was to compare the knowledge of and practices regarding tuberculosis in final-year medical students at schools from endemic and non-endemic areas. SUBJECTS: Final-year medical students at McMaster University in Canada, the Christian Medical College in India, and Makerere University in Uganda. METHODS: A questionnaire consisting of 20 multiple-choice questions assessing knowledge, practices, and exposure. A total knowledge score (maximum=13) and a total practice score (maximum=5) were created for each study site. RESULTS: 160 questionnaires were returned; the response rate was 68.4% (65/95) for McMaster University, 39.7% (23/58) for the Christian Medical College and 78.3% (72/92) for Makerere University. Students from Makerere University had the highest knowledge scores but differences were non-significant after adjustment for patient exposure and curriculum time (F(2,153)= 1.80, P=0.16). Differences in practice scores, however, remained significant after adjusting for curriculum time and patient exposure (F(2,153)=5.14, P=0.006). Knowledge score (F(1,156)=5.05, P=0.02), patient exposure (F(1,153)=9.11, P=0.003), and curriculum time and patient exposure (F(2,153)=5.14, P=0.006) were statistically significant positive predictors of the total practice score. CONCLUSIONS: This study demonstrated significant differences in undergraduate exposure to tuberculosis, total knowledge, and practice competency at three medical schools in Canada, India, and Uganda. In general, the knowledge base and practice competency of all three graduating classes was adequate.     

Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions

Cancer is often accompanied by worsening of the patient’s iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.     

Efficacy of albaconazole (UR-9825) in treatment of disseminated Scedosporium prolificans infection in rabbits

There are no effective therapeutics for treating invasive Scedosporium prolificans infections. Doses of 15, 25, and 50 mg/kg of body weight/day for the new triazole albaconazole (ABC) were evaluated in an immunocompetent rabbit model of systemic infection with this mold. Treatments were begun 1 day after challenge and given for 10 days. ABC at any dose was more effective than amphotericin B (AMB) at 0.8 mg/kg/day at clearing S. prolificans from tissue (P < 0.007). The percentages of survival at 25 mg of ABC/kg/day were similar to those obtained with AMB. Rabbits showed 100% survival when they were treated with 50 mg of ABC per kg (P < 0.0001 versus control group), and only this dosage was able to reduce tissue burden significantly in the five organs studied, i.e., spleen, kidneys, liver, lungs, and brain.     

De-escalation therapy in ventilator-associated pneumonia

OBJECTIVE: To evaluate de-escalation of antibiotic therapy in patients with ventilator-associated pneumonia. DESIGN: Prospective observational study during a 43-month period. SETTING: Medical-surgical intensive care unit. PATIENTS: One hundred and fifteen patients admitted to the intensive care unit with clinical diagnosis of ventilator-associated pneumonia. All the episodes of ventilator-associated pneumonia received initial broad-spectrum coverage followed by reevaluation according to clinical response and microbiology. Quantitative cultures obtained by bronchoscopic examination or tracheal aspirates were used to modify therapy. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty-one episodes of ventilator-associated pneumonia were diagnosed. Change of therapy was documented in 56.2%, including de-escalation (the most frequent cause) in 31.4% (increasing to 38% if isolates were sensitive). Overall intensive care unit mortality rate was 32.2%. Inappropriate antibiotic therapy was identified in 9% of cases and was associated with 14.4% excess intensive care unit mortality. Quantitative tracheal aspirates and bronchoscopic samples (58 protected specimen brush and three bronchoalveolar lavage) were associated with 32.7% and 29.5% intensive care unit mortality and 29.3% and 34.4% de-escalation rate. De-escalation was lower (p < .05) in the presence of nonfermenting Gram-negative bacillus (2.7% vs. 49.3%) and in the presence of late-onset pneumonia (12.5% vs. 40.7%). When the pathogen remained unknown, half of the patients died and de-escalation was not performed. CONCLUSION: De-escalation was the most important cause of antibiotic modification, being more feasible in early-onset pneumonia and less frequent in the presence of nonfermenting Gram-negative bacillus. The impact of quantitative tracheal aspirates or bronchoscopic techniques was comparable in terms of mortality.     

Ventilator-associated pneumonia: issues related to the artificial airway

Pooling of contaminated secretions above the cuff of the endotracheal tube predisposes patients to ventilator-associated pneumonia (VAP). Subglottic secretion drainage requires a special endotracheal tube that has a separate lumen that opens in the subglottic region above the tracheal tube. A recent meta-analysis of the 5 randomized clinical trials that evaluated the efficacy of removing these secretions found that this technique significantly reduces the incidence of VAP. One cost-effectiveness analysis showed savings of dollar 4,900 per episode of VAP prevented. Greatest benefit is derived by patients requiring fewer than 10 days of mechanical ventilation and not exposed to antibiotic therapy. Maintaining the intracuff pressure between 25 and 30 cm H2O is mandatory to guarantee effective drainage and safety. While silver-coated endotracheal tubes reduce pseudomonas pneumonia in intubated dogs and delay airway colonization in intubated patients, evaluation of studies with a variety of case mixes is warranted to identify subsets likely to benefit from the technique before it is implemented on a large scale. A patient who has a colonized airway and who undergoes percutaneous tracheotomy has an increased risk of VAP, particularly due to Pseudomonas aeruginosa, in the week following the procedure. As many studies suggest that incidence of VAP is highly dependent on the strategies of airway management, health care workers should be alerted to issues related to the artificial airway.     

Pneumonia caused by oxacillin-resistant Staphylococcus aureus treated with glycopeptides

OBJECTIVE: To determine whether ventilator-associated pneumonia caused by oxacillin-resistant Staphylococcus aureus (VAP-ORSA) treated with glycopeptides is associated with an increased mortality rate. DESIGN: Retrospective matched cohort study. SETTING: Four intensive care units in teaching hospitals. PATIENTS: Seventy-five patients were matched to 75 controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All adult intensive care unit patients with microbiologically documented VAP-ORSA were matched to intubated controls who did not develop VAP-ORSA, based on disease severity (Acute Physiology and Chronic Health Evaluation II score) at admission (+/-3 points), diagnostic category, and length of stay before pneumonia onset. Population characteristics and intensive care unit mortality rates of patients with VAP-ORSA and their controls without pneumonia were compared. Attributable mortality was determined by subtracting the crude mortality rate of controls from the crude mortality rate of VAP-ORSA patients. Thirty-six of the 75 matched VAP-ORSA patients died, representing a crude mortality rate of 48%, whereas 19 of the 75 controls died, a crude mortality rate of 25.3% (p < .01). Excess mortality was estimated to be 22.7% (95% confidence interval, 2.4-42.9%). Median length of intensive care unit stay in the surviving pairs was 33 days (interquartile range, 25-75%: 25-45 days) for VAP-ORSA patients and 21 days (interquartile range, 25-75%: 15-34.75 days) days for controls (p = .054). CONCLUSIONS: Despite appropriate glycopeptide therapy, there is an increased attributable mortality for pneumonia by ORSA, after careful adjustment for disease severity and diagnostic category.     

Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines

Standardized criteria for diagnosis and response assessment are needed to interpret and compare clinical trials and for approval of new therapeutic agents by regulatory agencies. Therefore, a National Cancer Institute–sponsored Working Group (NCI-WG) on chronic lymphocytic leukemia (CLL) published guidelines for the design and conduct of clinical trials for patients with CLL in 1988, which were updated in 1996. During the past decade, considerable progress has been achieved in defining new prognostic markers, diagnostic parameters, and treatment options. This prompted the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) to provide updated recommendations for the management of CLL in clinical trials and general practice.     

Stress by noise produces differential effects on the proliferation rate of radial astrocytes and survival of neuroblasts in the adult subgranular zone

The subgranular zone (SGZ) in the dentate gyrus contains radial astrocytes, known as Type-1 or Type-B cells, which generate neuroblasts (Type-2 cells or Type-D cells) that give rise to granular neurons. Stress increases glucocorticoid levels that target SGZ and modify the proliferation and apoptosis of hippocampal cells. Yet, it is not well-known whether stress differentially affects SGZ progenitors. We investigated the effects of noise-induced stress on the rate of proliferation and apoptosis of the Type-1 cells, Type-2 cells and newly generated granular neurons in the SGZ. We exposed Balb/C mice to noise using a standardized rodents' audiogram-fitted adaptation of a human noisy environment. We measured corticosterone serum levels at different time points. Animals received BrdU injections for 3 days and sequential sacrifices were done to carry out double-immunohistochemical analyses. We found that a 24-h noise exposure did not produce adaptative response in the curve of corticosterone as compared to a 12-h noise exposure. The percentage of BrdU+/GFAP+ cells was significantly reduced in the stress group as compared to controls. A high proportion of CASP-3+/GFAP+ radial astrocytes were found in the stress group. The percentage of BrdU+/doublecortin+ cells was higher in controls than in the stress group. Interestingly, the apoptosis rate of doublecortin-expressing cells in the stress group was slightly lesser than in controls. Remarkably, we did not find significant differences in the number of BrdU+/NeuN+ and CASP-3+/NeuN+ neurons. These data indicate that stress differentially affects the rate of proliferation and apoptosis in SGZ progenitors and suggest a possible compensatory mechanism to keep the net number of granular neurons.     

Preservation of glial cytoarchitecture from ex vivo human tumor and non-tumor cerebral cortical explants: A human model to study neurological diseases

For the human brain, in vitro models that accurately represent what occurs in vivo are lacking. Organotypic models may be the closest parallel to human brain tissue outside of a live patient. However, this model has been limited primarily to rodent-derived tissue. We present an organotypic model to maintain intraoperatively collected human tumor and non-tumor explants ex vivo for a prolonged period of time ( approximately 11 days) without any significant changes to the tissue cytoarchitecture as evidenced through immunohistochemistry and electron microscopy analyses. The ability to establish and reliably predict the cytoarchitectural changes that occur with time in an organotypic model of tumor and non-tumor human brain tissue has several potential applications including the study of cell migration on actual tissue matrix, drug toxicity on neural tissue and pharmacological treatment for brain cancers, among others.