Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study

Background

Bloodstream infection is a common cause of hospitalization, morbidity and death in children. The impact of antimicrobial resistance and HIV infection on outcome is not firmly established.

Methods

We assessed the incidence of bloodstream infection and risk factors for fatal outcome in a prospective cohort study of 1828 consecutive admissions of children aged zero to seven years with signs of systemic infection. Blood was obtained for culture, malaria microscopy, HIV antibody test and, when necessary, HIV PCR. We recorded data on clinical features, underlying diseases, antimicrobial drug use and patients' outcome.

Results

The incidence of laboratory-confirmed bloodstream infection was 13.9% (255/1828) of admissions, despite two thirds of the study population having received antimicrobial therapy prior to blood culture. The most frequent isolates were klebsiella, salmonellae, Escherichia coli, enterococci and Staphylococcus aureus. Furthermore, 21.6% had malaria and 16.8% HIV infection. One third (34.9%) of the children with laboratory-confirmed bloodstream infection died. The mortality rate from Gram-negative bloodstream infection (43.5%) was more than double that of malaria (20.2%) and Gram-positive bloodstream infection (16.7%). Significant risk factors for death by logistic regression modeling were inappropriate treatment due to antimicrobial resistance, HIV infection, other underlying infectious diseases, malnutrition and bloodstream infection caused by Enterobacteriaceae, other Gram-negatives and candida.

Conclusion

Bloodstream infection was less common than malaria, but caused more deaths. The frequent use of antimicrobials prior to blood culture may have hampered the detection of organisms susceptible to commonly used antimicrobials, including pneumococci, and thus the study probably underestimates the incidence of bloodstream infection. The finding that antimicrobial resistance, HIV-infection and malnutrition predict fatal outcome calls for renewed efforts to curb the further emergence of resistance, improve HIV care and nutrition for children.     

A crucial role for TNF-α in mediating neutrophil influx induced by endogenously generated or exogenous chemokines,KC/CXCL1 and LIX/CXCL5

Background and purpose:

Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice.

Experimental approach:

Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-α. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by elisa. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy.

Key results:

Antigen challenge induced dose- and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-α, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-α antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose- and time-dependent neutrophil recruitment and TNF-α production, which were inhibited by reparixin or anti-TNF-α treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-α upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-α or anti-LIX/CXCL5.

Conclusion and implications:

Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-α, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.     

Can a Chronic Care Model Collaborative Reduce Heart Disease Risk in Patients with Diabetes?

BACKGROUND: There is a need to identify effective practical interventions to decrease cardiovascular disease risk in patients with diabetes. OBJECTIVE: We examine the impact of participation in a collaborative implementing the chronic care model (CCM) on the reduction of cardiovascular disease risk in patients with diabetes. DESIGN: Controlled pre- and postintervention study. PATIENTS/PARTICIPANTS: Persons with diabetes receiving care at 13 health care organizations exposed to the CCM collaborative and controls receiving care in nonexposed sites. MEASUREMENTS AND MAIN RESULTS: Ten-year risk of cardiovascular disease; determined using a modified United Kingdom Prospective Diabetes Study risk engine score. A total number of 613 patients from CCM intervention sites and 557 patients from usual care control sites met the inclusion criteria. The baseline mean 10-year risk of cardiovascular disease was 31% for both the intervention group and the control group. Participants in both groups had improved blood pressure, lipid levels, and HbA1c levels during the observation period. Random intercept hierarchical regression models showed that the intervention group had a 2.1% (95% CI -3.7%, -0.5%) greater reduction in predicted risk for future cardiovascular events when compared to the control group. This would result in a reduced risk of one cardiovascular disease event for every 48 patients exposed to the intervention. CONCLUSIONS: Over a 1-year interval, this collaborative intervention using the CCM lowered the cardiovascular disease risk factors of patients with diabetes who were cared for in the participating organization's settings. Further work could enhance the impact of this promising multifactorial intervention on cardiovascular disease risk reduction.     

Neighborhood of Residence is Associated with Daily Adherence to CPAP Therapy

Study Objectives:

Adherence to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea is poor. Risk factors for nonadherence are not well understood but may reflect individual or neighborhood socioeconomic factors. We sought to determine the association of socioeconomic status and initial CPAP adherence.

Design:

Retrospective cohort study, 2005 to 2006.

Setting:

Philadelphia VA Medical Center.

Participants:

Of 330 consecutive veterans who met study criteria for initiation of CPAP therapy for newly diagnosed sleep apnea, 266 had complete data for study inclusion.

Interventions:

N/A.

Measurements:

Through a multivariable logistic regression model, using an outcome of objectively measured CPAP use ≥ 4 h daily during the first week of treatment, we tested whether patients from higher socioeconomic neighborhoods had higher CPAP adherence. We measured neighborhood socioeconomic status with an index derived from the 2000 U.S. Census at the block group-level composed of median household income, male and female employment, adult high school completion, married households, and minority composition.

Results:

CPAP adherence ≥ 4 h occurred on 48.9% of 1,805 patient-days observed for the 266 subjects. After adjustment for individual sociodemographic characteristics and medical comorbidity, the probability of daily CPAP use ≥ 4 h ranged from 34.1% (95% CI, 26.4–42.7) for subjects from a low socioeconomic neighborhood (5th percentile) to 62.3% (95% CI, 53.8–70.1) for subjects from a high (95th percentile) neighborhood.

Conclusions:

In a retrospective cohort of veterans, initial CPAP adherence was closely associated with higher neighborhood socioeconomic factors. Future investigation should target specific impediments to adherence in the home and neighborhood environment.

Citation:

Platt AB; Field SH; Asch DA; Chen Z; Gupta R; Roche DF; Gurubhagavatula I; Christie JD; Kuna ST. Neighborhood of residence is associated with daily adherence to CPAP therapy. SLEEP 2009;32(6):799-806.     

Cytopathological and chemico‐physical analyses of smears of mucosa surrounding oral piercing

Oral Diseases (2010) 16 , 160–166 Objective: The aim of this comparative study was to analyze cytopathologically and chemico‐physically the mucosa surrounding oral piercing to correlate results with adverse tissue signs. Materials and methods: The tongue superficial mucosa of 15 young subjects (control group) and the superficial mucosa surrounding oral piercing of 15 young subjects (test group, TG) were smeared on slides, Papanicolaou stained and analyzed under the optical microscope. Some smears were prepared for (back‐scattered) scanning electron microscope (SEM) and X‐ray microanalysis to study piercing fragments. Results: Smears of TG displayed a variable extent of bacterial cytolysis of epithelial cells, fungi, hyperkeratosis, parakeratosis, granulocyte infiltration, calcium formations and bacterial flora; the four last statistically significant (P < 0.05). Foreign bodies surrounded by keratinocytes were detected under both light and SEM. X‐ray microanalyses highlighted piercing alloy aggression, ion release and an inverse gradient of ion concentration inside keratinocytes. Conclusions: The pathological findings in smears correlated with adverse effects of oral piercing. Ion release may be related to direct toxic effects and belated reactions because of metal sensitization. A strict regulation of piercing is warranted.     

Olfaction in dentistry

Oral Diseases (2010) 16 , 221–232 Practitioners of oral medicine frequently encounter patients with complaints of taste disturbance. While some such complaints represent pathological processes specific to the gustatory system, per se, this is rarely the case. Unless taste‐bud mediated qualities such as sweet, sour, bitter, salty, umami, chalky, or metallic are involved, ‘taste’ dysfunction inevitably reflects damage to the sense of smell. Such ‘taste’ sensations as chicken, chocolate, coffee, raspberry, steak sauce, pizza, and hamburger are dependent upon stimulation of the olfactory receptors via the nasopharynx during deglutition. In this paper, we briefly review the anatomy, physiology, and pathophysiology of the olfactory system, along with means for clinically assessing its function. The prevalence, etiology, and nature of olfactory disorders commonly encountered in the dental clinic are addressed, along with approaches to therapy and patient management.     

Virulence of major periodontal pathogens and lack of humoral immune protection in a rat model of periodontal disease

Oral Diseases (2010) 16 , 686–695 Objective: This study was designed to test the hypothesis that periodontal pathogens Tannerella forsythia and Porphyromonas gingivalis are synergistic in terms of virulence potential using a model of mixed‐microbial infection in rats. Materials and methods: Three groups of rats were infected orally with either T. forsythia or P. gingivalis in mono‐bacterial infections or as mixed‐microbial infections for 12 weeks and a sham‐infected group were used as a control. This study examined bacterial infection, inflammation, immunity, and alveolar bone loss changes with disease progression. Results: Tannerella forsythia and P. gingivalis genomic DNA was detected in microbial samples from infected rats by PCR indicating their colonization in the rat oral cavity. Primary infection induced significantly high IgG, IgG2b, IgG1, and IgG2a antibody levels indicating activation of mixed Th1 and Th2 immune responses. Rats infected with the mixed‐microbial consortium exhibited significantly increased palatal horizontal and interproximal alveolar bone loss. Histological examinations indicated significant hyperplasia of the gingival epithelium with moderate inflammatory infiltration and apical migration of junctional epithelium. The results observed differ compared to uninfected controls. Conclusion: Our results indicated that T. forsythia and P. gingivalis exhibit virulence, but not virulence synergy, resulting in the immuno‐inflammatory responses and lack of humoral immune protection during periodontitis in rats.     

Factors influencing the regional haemodynamic responses to methanandamide and anandamide in conscious rats

Background and purpose:

In vitro evidence suggests that metabolism of anandamide by cyclooxygenase-2 (COX-2) may be more important when the primary metabolic pathway [i.e. fatty acid amide hydrolase (FAAH)] is inhibited. Thus, the first aim of the present study was to assess the effects of COX-2 and/or FAAH inhibition, on the cardiovascular actions of anandamide. The second aim was to compare the effects of anandamide with those of the metabolically stable analogue (i.e. methanandamide) and investigate mechanisms involved in responses to the latter in conscious rats.

Experimental approach:

Rats were chronically instrumented for recording blood pressure, heart rate and renal, mesenteric and hindquarters vascular conductances in the freely moving state.

Key results:

Inhibition of FAAH with URB597 (cyclohexycarbamic acid 3′-carbamoyl-biphenyl-3-yl-ester) augmented the haemodynamic actions of anandamide, but there was no effect of COX-2 inhibition with parecoxib, either in the absence or the presence of URB597. Methanandamide caused CB₁ receptor-mediated renal and mesenteric vasoconstriction and evoked β₂-adrenoceptor-mediated hindquarters vasodilatation.

Conclusions and implications:

No evidence for an involvement of COX-2 in the systemic cardiovascular actions of anandamide could be demonstrated. Vasoconstrictor actions of methanandamide were shown to involve CB₁ receptors, whereas no involvement of CB₁ receptors in such actions of anandamide has been shown. However, β₂-adrenoceptor-mediated hindquarters vasodilatation, independent of CB₁ receptors, observed here with methanandamide, has previously been seen with anandamide and differs from previous results with other synthetic cannabinoids for which the response was CB₁ receptor-dependent. Thus, mechanisms underlying the cardiovascular actions of endocannabinoids and synthetic analogues appear to be agonist-specific.     

Comparison of mechanical and electrical activity and interstitial cells of Cajal in urinary bladders from wild-type and W/Wv mice

Background and purpose:

W/W^v and wild-type murine bladders were studied to determine whether the W/W^v phenotype, which causes a reduction in, but not abolition of, tyrosine kinase activity, is a useful tool to study the function of bladder interstitial cells of Cajal (ICC).

Experimental approach:

Immunohistochemistry, tension recordings and microelectrode recordings of membrane potential were performed on wild-type and mutant bladders.

Key results:

Wild-type and W/W^v detrusors contained c-Kit- and vimentin-immunopositive cells in comparable quantities, distribution and morphology. Electrical field stimulation evoked tetrodotoxin-sensitive contractions in wild-type and W/W^v detrusor strips. Atropine reduced wild-type responses by 50% whereas a 25% reduction occurred in W/W^v strips. The atropine-insensitive component was blocked by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both tissue types. Wild-type and W/W^v detrusors had similar resting membrane potentials of −48 mV. Spontaneous electrical activity in both tissue types comprised action potentials and unitary potentials. Action potentials were nifedipine-sensitive whereas unitary potentials were not. Excitatory junction potentials were evoked by single pulses in both tissues. These were reduced by atropine in wild-type tissues but not in W/W^v preparations. The atropine-insensitive component was abolished by pyridoxal-5-phosphate-6-azophenyl-2′,4′-disulphonic acid in both preparations.

Conclusions and implications:

Bladders from W/W^v mice contain c-Kit- and vimentin-immunopositive ICC. There are similarities in the electrical and contractile properties of W/W^v and wild-type detrusors. However, significant differences were found in the pharmacology of the responses to neurogenic stimulation with an apparent up-regulation of the purinergic component. These findings indicate that the W/W^v strain may not be the best model to study ICC function in the bladder.     

Terrorism-Related Fear and Avoidance Behavior in a Multiethnic Urban Population

Objectives. We sought to determine whether groups traditionally most vulnerable to disasters would be more likely than would be others to perceive population-level risk as high (as measured by the estimated color-coded alert level) would worry more about terrorism, and would avoid activities because of terrorism concerns.Methods. We conducted a random digit dial survey of the Los Angeles County population October 2004 through January 2005 in 6 languages. We asked respondents what color alert level the country was under, how often they worry about terrorist attacks, and how often they avoid activities because of terrorism. Multivariate regression modeled correlates of worry and avoidance, including mental illness, disability, demographic factors, and estimated color-coded alert level.Results. Persons who are mentally ill, those who are disabled, African Americans, Latinos, Chinese Americans, Korean Americans, and non-US citizens were more likely to perceive population-level risk as high, as measured by the estimated color-coded alert level. These groups also reported more worry and avoidance behaviors because of concerns about terrorism.Conclusions. Vulnerable populations experience a disproportionate burden of the psychosocial impact of terrorism threats and our national response. Further studies should investigate the specific behaviors affected and further elucidate disparities in the disaster burden associated with terrorism and terrorism policies.One public health definition of terrorism proposes that the effects of terrorism “real or threatened” may include “adverse health effects in those immediately affected and their community, ranging from a loss of well-being or security to injury, illness, or death.”¹ The events of September 11, 2001, influenced well-being and security beyond the regions directly attacked.^2–4 Many people throughout the United States felt they were at risk from terrorism. Risk perceptions, along with antiterrorism programs, laws, and policies (e.g., airport security regulations, visa restrictions, and warrantless surveillance) affected Americans’ lifestyles and behaviors. In the months following the attacks, 40% to 50% of US adults still feared for their safety^4,5 and 11% reported changed behaviors such as avoiding public gatherings.^6,7Risk perception theories and research posit that individuals assess risks based on a balance of many factors, including the probability of a hazard or risk personally affecting them, the severity of the personal consequences from risk exposure, feelings of personal control, the perceived inequality of risk distribution across society, and trust in institutions managing risks.^8,9 For instance, a national survey conducted 2 months after the attacks of September 11 found that the distance between one''s home and the World Trade Center was inversely correlated with perceptions of terrorism risk among non-Hispanic Whites.⁹ By contrast, Latinos’ and African Americans’ judgments of future terror risks were not affected by how far they lived from New York City.These results are consistent with findings of lower risk perceptions among politically conservative White males, who feel greater control over their environment and greater trust in the institutions protecting them.¹⁰ As noted by Fischhoff,

The processes determining terror risks are so complex and poorly understood (by experts, much less the general public) that all citizens might feel equally at risk. On the other hand, people might use even rudimentary theories of terrorism to derive differential predictions of vulnerability: Who are the terrorists’ targets? Who can take effective protective action?^{9(pp 137–138)}

The estimation of personal risk and vulnerability to terrorism may act as a key motivator to behavioral adaptations, including avoidance of usual activities or increased adoption of protective behaviors.^11–14 Those who believe they are particularly vulnerable to a risk may be motivated to perform risk reduction. Studies document that vulnerable populations, such as the chronically ill, the physically disabled, non-White racial/ethnic minorities, and immigrants, bear a disproportionate burden of harm from natural disasters^15–18 and that there are racial/ethnic differences in perceived risks of natural disasters.¹⁵Similarly, research finds specifically that African Americans and Latinos perceive they are at greater risk from terrorism than do non-Latino Whites.^9,19 A survey conducted less than a year after September 11, 2001, reported that African Americans were most likely to limit their outside activities and change their mode of transportation in response to fears of terrorism.⁵ Also, a national survey found that persons with disabilities were more anxious about their personal risk from terrorism than were persons without disabilities, even when equally prepared.²⁰ Another study reported that persons who increased their disaster preparations in response to the possibility of terrorist attacks included African Americans, Latinos, persons with disabilities or household dependents, and non–US-born populations.²¹As with health and disasters generally, these populations may experience disparities in the effects of terrorism and terrorism policies including their risk perceptions and avoidant behavior. An Israeli survey found that large social groups, including women, had adapted their daily behaviors to minimize the impact of terrorism risks.¹⁴ As studies continue to document the long-term and indirect health effects of the September 11 attacks, it remains important to understand how long these risk perceptions and behavioral effects have lasted and who has been most affected.^22–27The Homeland Security Advisory System (HSAS) is a post–September 11 program that may influence risk perceptions and avoidant behavior—although that is not its intended purpose. The HSAS announces the Department of Homeland Security''s assessed risk of a terrorist attack on the United States via a color-coded threat level and disseminates information regarding that level''s risk to public safety officials and the general public. The HSAS has 5 color-coded conditions: green, blue, yellow, orange, and red corresponding to threat levels of low, guarded, elevated, high, and severe, respectively. At each level are recommended actions for the public and government agencies to implement to reduce the “likelihood or impact of an attack.”²⁸ The value of the HSAS is debated, considering its adverse effects on well-being caused by unnecessarily raising fears and anxieties.^29–31 To our knowledge, there are no studies examining how vulnerable groups perceive the HSAS alert level, an important issue for researchers interested in disaster vulnerability and how population characteristics affect perceptions of overall population risk.We examined how the characteristics of a population affect its overall, population-level risk perceptions, worry about terrorism, and avoidance of certain activities as a result of terrorism concerns, focusing on these outcomes in vulnerable population groups. Three sets of hypotheses underlay our study. We hypothesized that vulnerable populations would be most likely to perceive population-level risk as high, as measured by the estimated HSAS level. Although there is little systematic study of this topic, previous US studies have documented disparities in terrorism fears by gender, race, ethnicity, and education level. We studied 4 vulnerable groups of interest to public health and policy officials: persons with mental illness, persons with disabilities, non-White racial/ethnic groups, and immigrants. We hypothesized that vulnerable groups would be most likely to fear terrorism and would avoid activities because of terrorism fears. We also hypothesized persons who estimated the HSAS level to be red (severe) or orange (high) at the time of the survey, when the HSAS level was yellow (elevated), would report greater worry about terrorism and greater avoidance of activities as a result of terrorism concerns.