A data-driven allocation tool for in-kind resources distributed by a state health department.

OBJECTIVE: The objective of this study was to leverage a state health department's operational data to allocate in-kind resources (children's car seats) to counties, with the proposition that need-based allocation could ultimately improve public health outcomes. METHODS: This study used a retrospective analysis of administrative data on car seats distributed to counties statewide by the Georgia Department of Public Health and development of a need-based allocation tool (presented as interactive supplemental digital content, adaptable to other types of in-kind public health resources) that relies on current county-level injury and sociodemographic data. RESULTS: Car seat allocation using public health data and a need-based formula resulted in substantially different recommended allocations to individual counties compared to historic distribution. CONCLUSIONS: Results indicate that making an in-kind public health resource like car seats universally available results in a less equitable distribution of that resource compared to deliberate allocation according to public health need. Public health agencies can use local data to allocate in-kind resources consistent with health objectives; that is, in a manner offering the greatest potential health impact. Future analysis can determine whether the change to a more equitable allocation of resources is also more efficient, resulting in measurably improved public health outcomes.

The influence of lunar phases on the occurrence of myocardial infarction: fact or myth? The MONICA/KORA Myocardial Infarction Registry.

AIMS: The potential influence of lunar phases on the occurrence of myocardial infarction is still controversial. The purpose of the present study was to investigate the association of the lunar cycle on the occurrence of fatal and non-fatal myocardial infarction based on a myocardial infarction registry. METHODS AND RESULTS: We studied 15,985 patients consecutively hospitalised with an acute myocardial infarction (AMI) between 1 January 1985 and 31 December 2007 with a known date of symptom onset who were recruited from a population-based myocardial infarction registry. The exact hour of AMI onset was known for 9813 events. Poisson regression analysis was performed to examine the relation between the lunar cycle and the occurrence of AMI. There was no association between new moon, full moon, waning moon and waxing moon and the occurrence of AMI. However, we observed that the three days after a new moon may be significantly protective for the occurrence of AMI, rate ratio (RR) 0.94 (95% CI 0.91-0.98), and the day before a new moon had a slightly negative effect (RR 1.06, 95% CI 1.00-1.12). Stratified analysis did not reveal any susceptible subgroups. CONCLUSION: The moon phases did not show any apparent association with AMI occurrence. However, there might be a 'cardioprotective' time three days after a new moon.

Patient-reported symptoms in acute myocardial infarction: differences related to ST-segment elevation: the MONICA/KORA Myocardial Infarction Registry.

OBJECTIVES: The early recognition of symptoms of myocardial infarction (MI) is crucial for patients with both ST-segment elevation (STEMI) and non-STEMI (NSTEMI). However, to date, only a few studies have examined the differences between patients with STEMI and NSTEMI with regard to the range of presenting MI symptoms. DESIGN: The study population comprised 889 individuals with STEMI and 1268 with NSTEMI, aged 25-74, hospitalized with a first-time MI between January 2001 and December 2006 recruited from a population-based MI registry. The occurrence of 13 symptoms was recorded during a standardized patient interview. RESULTS: Patients with STEMI were significantly younger, more likely to be smokers and less likely to have a history of hypertension or sleep disturbances prior to the acute MI (AMI) event than those with NSTEMI. A total of 50% of the patients attributed their experienced symptoms to the heart. Logistic regression modelling revealed that patients with STEMI were significantly more likely than patients with NSTEMI to complain of vomiting [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.76-3.05], dizziness (OR 1.63, 95% CI 1.30-2.03) and diaphoresis (OR 1.49, 95% CI 1.23-1.81). Furthermore, patients with STEMI were less likely to experience dyspnoea (OR 0.81, 95% CI 0.68-0.98) or pain in the throat/jaw (OR 0.80, 95% CI 0.66-0.98). CONCLUSIONS: Only half of all patients correctly attributed their symptoms to the heart. Patients with STEMI and NSTEMI showed differences regarding several presenting symptoms. Further research is needed to replicate our results, and public awareness of AMI symptoms needs to be improved.

[Multimorbidity and successful aging: the population-based KORA-Age study]. / Multimorbidität und erfolgreiches Altern: Ein Blick auf die Bevölkerung im Rahmen der KORA-Age-Studie.

BACKGROUND: The objective of the KORA-Age research consortium is to assess the determinants and consequences of multimorbidity in the elderly and to look into reasons for successful aging in the general public. PATIENTS AND METHODS: In the KORA-Age cohort study 9,197 persons were included who where born in the year 1943 or before and participants of previous KORA cohort studies conducted between 1984 and 2001 (KORA: Cooperative Health Research in the Region of Augsburg). The randomized intervention study KORINNA (Coronary infarct follow-up treatment in the elderly) tested a nurse-based case management program with 338 patients with myocardial infarct and included an evaluation in health economics. RESULTS: A total of 2,734 deaths were registered, 4,565 participants submitted a postal health status questionnaire and 4,127 participants were interviewed by telephone (response 76.2% and 68.9% respectively). A gender and age-stratified random sample of the cohort consisting of 1,079 persons took part in a physical examination (response 53.8%). CONCLUSION: The KORA-Age consortium was able to collect data in a large population-based sample and is contributing to the understanding of multimorbidity and successful aging.

Effects of oxygen, growth state, and senescence on the antioxidant responses of WI-38 fibroblasts.

Mitotically active, growth-arrested cells and proliferatively senescent cultures of human fetal lung fibroblasts (WI-38) were exposed to six different oxygen tensions for various lengths of time and then analyzed to determine the responses of their antioxidant defense system. Glutathione (GSH) concentration increased as a function of ambient oxygen tension in early passage cultures; the effect was larger in exponentially growing cultures than in those in a state of contact-inhibited growth arrest, but was absent in senescent cells. Conversely, the activity of glutathione disulfide reductase was greater in growth-arrested cultures than in mitotically active cells irrespective of oxygen tension. Glucose-6-phosphate dehydrogenase was lowest in log-phase cells exposed to different oxygen tensions for 24 h and in senescent cells. Both hypoxia and hyperoxia depressed selenium-dependent glutathione peroxidase activity in early passage cultures, while the activity of the enzyme progressively declined with increasing oxygen in senescent cells. The GSH S-transferase activity was unresponsive to changes in ambient oxygen tension in either young or senescent cultures. Manganese-containing superoxide dismutase (MnSOD) activity was unaffected by oxygen tension, but was elevated in young confluent cultures as compared with cultures in log-phase growth. MnSOD activity was significantly higher in senescent cultures than in early passage cultures and was also responsive to increased oxygen tension in senescent cultures. Copper-zinc-containing superoxide dismutases activity was not affected by oxygen tension or the passage of time, but it declined in senescent cultures.

Hyperbaric oxygen protects from sepsis mortality via an interleukin-10-dependent mechanism.

OBJECTIVE: This study was performed to determine whether hyperbaric oxygen (HBO2) therapy is protective in cecal ligation and puncture (CLP)-induced sepsis and if protection is dependent on oxygen dosing. We also wished to determine whether HBO2 affected bacterial clearance or altered macrophage production of interleukin-10 (IL-10)s in the setting of CLP sepsis. Finally, we wished to determine whether the mechanism of HBO2 protection in sepsis was dependent on IL-10 production. DESIGN: Prospective, experimental study. SETTING: University experimental research laboratory. SUBJECTS: C57BL/6 and C57BL/6 IL-10 mice. INTERVENTIONS: Sepsis was induced by CLP. Mice were randomized to receive a 1.5-hr HBO2 treatment at either 1, 2.5, or 3 atmospheres absolute every 12 hrs or HBO2 at 2.5 atmospheres absolute every 24 hrs. Mice were also harvested at 24 hrs for determination of bacterial load and isolation and study of CD11b peritoneal macrophages. MEASUREMENTS AND MAIN RESULTS: Survival was monitored for 100 hrs after CLP +/- HBO2 treatment. HBO2 significantly improved survival when administered at 2.5 atmospheres absolute every 12 hrs. Other treatment schedules were not protective, and treatment at 3.0 atmospheres absolute significantly worsened survival outcome. Bacterial load was significantly reduced in splenic homogenates but not peritoneal fluid at 24 hrs. Macrophages isolated from HBO2-treated mice demonstrated enhanced IL-10 secretion in response to lipopolysaccharide as compared with CLP controls. Mice genetically deficient in IL-10 expression treated with HBO2 at 2.5 atmospheres absolute every 12 hrs were not protected from CLP-induced mortality. CONCLUSION: HBO2 may be protective in CLP sepsis within a window of oxygen dosing. The mechanism of HBO2 protection may be potentially linked in part to expression of IL-10, as peritoneal macrophages demonstrated enhanced IL-10 expression and IL-10 mice were not protected by HBO2 treatment.

Troglitazone-induced changes in adiponectin do not affect endothelial function in diabetes.

OBJECTIVE: Adiponectin has been proposed to be related to endothelial function. We have examined the relationship between the increase in adiponectin levels that is associated with troglitazone treatment and endothelium-dependent vasodilation in type 2 diabetic patients. RESEARCH METHODS AND PROCEDURES: Seventy-two patients participated in this randomized, placebo-controlled, double-blinded study. High-resolution ultrasound images were used to measure the flow-mediated dilation (endothelium-dependent) and nitroglycerin-induced dilation (endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was employed to measure the vascular reactivity in the forearm skin. RESULTS: Troglitazone treatment resulted in an average 75% increase in the adiponectin levels, but no changes were observed in the endothelium-dependent vasodilation, any other measurement of vascular reactivity, or any other markers of endothelial activation. Also, no changes were observed in the expression of the receptor for advanced glycation end-products in skin biopsies taken from the forearm. Significant correlations were observed during troglitazone treatment between the changes in the adiponectin levels and the changes in fasting plasma glucose (r = -0.29, p < 0.05), hemoglobin A(1c) (r = -0.30, p < 0.05), total cholesterol (r = 0.25, p < 0.05), and low-density lipoprotein-cholesterol (r = 0.34, p < 0.01). DISCUSSION: The increase in adiponectin levels after troglitazone treatment is not associated with an improvement in the endothelium-dependent vasodilation, indicating that adiponectin is not a major determinant of endothelial function. In addition, receptor for advanced glycation end-products expression in the skin microcirculation is not affected by troglitazone treatment.

Gastrointestinal ischemia-reperfusion injury is lectin complement pathway dependent without involving C1q.

Complement activation plays an important role in local and remote tissue injury associated with gastrointestinal ischemia-reperfusion (GI/R). The role of the classical and lectin complement pathways in GI/R injury was evaluated using C1q-deficient (C1q KO), MBL-A/C-deficient (MBL-null), complement factor 2- and factor B-deficient (C2/fB KO), and wild-type (WT) mice. Gastrointestinal ischemia (20 min), followed by 3-h reperfusion, induced intestinal and lung injury in C1q KO and WT mice, but not in C2/fB KO mice. Addition of human C2 to C2/fB KO mice significantly restored GI/R injury, demonstrating that GI/R injury is mediated via the lectin and/or classical pathway. Tissue C3 deposition in C1q KO and WT, but not C2/fB KO, mice after GI/R demonstrated that complement was activated in C1q KO mice. GI/R significantly increased serum alanine aminotransferase, gastrointestinal barrier dysfunction, and neutrophil infiltration into the lung and gut in C1q KO and WT, but not C2/fB KO, mice. MBL-null mice displayed little gut injury after GI/R, but lung injury was present. Addition of recombinant human MBL (rhuMBL) to MBL-null mice significantly increased injury compared with MBL-null mice after GI/R and was reversed by anti-MBL mAb treatment. However, MBL-null mice were not protected from secondary lung injury after GI/R. These data demonstrate that C2 and MBL, but not C1q, are necessary for gut injury after GI/R. Lung injury in mice after GI/R is MBL and C1q independent, but C2 dependent, suggesting a potential role for ficolins in this model.

Inhibition of C5 or absence of C6 protects from sepsis mortality.

Inhibiting complement anaphlytoxin C5a during sepsis may prevent sepsis mortality. Although human anti-C5 antibodies exist, their therapeutic use in microbial sepsis has been avoided because of the hypothesis that inhibiting C5b will prevent formation of the bactericidal membrane attack complex (MAC) and worsen clinical outcome. We wished to test the hypothesis that inhibition of C5 would improve outcomes in sepsis. Sepsis was induced in rats by laparotomy and cecal ligation and puncture (CLP) by an IACUC-approved protocol. Sham animals underwent laparotomy without CLP. Following CLP rats were randomized to receive a single IV dose of purified IgG ant-C5 antibody (Ab) or control IgG Ab. Anti-C5 Ab treated rats (n = 20) had significantly lower mortality vs. controls (n = 21), 20% vs. 52% (P = 0.019, log-rank). Analysis of bacterial load by culture of spleen and liver homogenates showed a reduction in colony forming units in anti-C5 Ab treated rats vs. control IgG (P = 0.003 and 0.009, respectively). Anti-C5 treatment reduced lung injury as measured by total MPO content of lung tissue (P = 0.024). Finally, rats genetically deficient in C6 production, unable to form MAC but capable of producing C5a and C5b, were protected from CLP-induced sepsis mortality. Our results show that in anti-C5 antibody therapy prevents CLP sepsis-induced mortality and improves lung injury. Inhibition of the complement MAC does not increase bacterial load or mortality, therefore, the use of anti-C5 therapy may be beneficial rather than detrimental in sepsis.

ECM-stimulated signaling and actin reorganization in embryonic corneal epithelia are Rho dependent.

PURPOSE: The goal of this study was to investigate the role of the small guanosine triphosphatase (GTPase), Rho, in the corneal epithelial response to extracellular matrix (ECM) molecules. The avian corneal epithelial model was used to establish that Rho is required for actin reorganization and tyrosine phosphorylation of integrin-mediated signal pathway proteins. METHODS: Whole embryonic corneal epithelia were isolated without the basal lamina and either transfected with Rho-specific antisense oligonucleotides or treated with Clostridium botulinum C3 exoenzyme and then stimulated with fibronectin (FN) or collagen (COL). The epithelia were evaluated for actin reorganization and protein production including Rho protein levels and tyrosine phosphorylation with Western blot analysis. RESULTS: After an overnight transient transfection with antisense oligonucleotides, Rho protein levels were decreased more than 80%, and tyrosine phosphorylation of all integrin-mediated signal transduction proteins was decreased compared with control epithelia. Intracellular Rho distribution did not change in the presence of antisense oligonucleotides; however, the amount of immunolabeled Rho decreased. Disrupting the signaling cascade with Rho antisense also blocked FN- and COL-stimulated actin cortical mat reformation. C. botulinum C3 exoenzyme, a pharmacologic agent that specifically causes adenosine diphosphate (ADP) ribosylation and inactivation of Rho, also blocked actin reorganization and tyrosine phosphorylation. In contrast, decreasing Raf protein levels did not change FN-mediated actin reorganization or tyrosine phosphorylation. CONCLUSIONS: Decreasing Rho protein or blocking its function inhibited ECM-stimulated actin reorganization and signal transduction, as measured by tyrosine phosphorylation.

Approaches to studying cellular signaling: a primer for morphologists.

Many research projects will lead to understanding tissue and/or cell responses to extracellular influences either from soluble factors or the surrounding extracellular matrix. These types of investigations will require the understanding of signal transduction. This particular cell biological field has literally exploded with information and new technical approaches in the past 10 years. This article is directed toward investigators interested in using these new approaches to study their systems. An overview of the general principles of signal transduction events including the types of receptors and intracellular signaling events is followed by an introduction to methods for visualizing signal transduction. This is followed by an introduction to biochemical analysis and an example of combining several approaches to understanding a tissue response to extracellular matrix stimulus.

Effect of a silver device in preventing catheter-related infections in peritoneal dialysis patients: silver ring prophylaxis at the catheter exit study.

Catheter-related infections remain a significant cause of method failure in chronic peritoneal dialysis (PD) therapy. Given the increasing antibiotic resistance, such nonpharmacological strategies as local silver devices attract more interest. To establish whether a silver ring device (designed by Grosse-Siestrup in 1992) mounted onto the PD catheter and placed at the exit site at skin level is effective in preventing exit-site and other catheter-related infections, a prospective 12-month, multicenter, controlled study stratified by diabetes status was conducted. The study subjects were assessed by an extensive structured inventory, including a broad spectrum of control variables, such as age, body mass index (BMI), Staphylococcus aureus carrier status, catheter features, mode and quality of PD therapy, comorbidity, and psychosocial rehabilitation. Ten experienced German outpatient dialysis centers (seven adult, three pediatric) participated in the trial. All eligible patients (n=195) from the study area without catheter-related infections during the ascertainment period were included (incidental subjects undergoing PD therapy for at least 3 months). The main outcome measures were the occurrence of first exit-site infections (primary study end point), sinus tract/tunnel infection, and peritonitis. Ninety-seven patients were assigned to the silver ring and 98 patients to the control group. Baseline characteristics of age, sex, proportion of pediatric and incidental patients, S aureus carrier status, and other variables were similar in both groups. The incidence of infections in the silver ring group versus the control group was as follows: 23 of 97 versus 16 of 98 patients had exit-site infections, 12 of 97 versus 12 of 98 patients had sinus tract/tunnel infections, 16 of 97 versus 18 of 98 patients had peritonitis, respectively. Kaplan-Meier analysis for the probability of an infection-free interval showed no statistical difference (log-rank test) between the two groups. Displacement of the silver ring contributed to study termination in 6% of the study group patients, including two patients with catheter loss. Univariate analysis and multiple logistic regression identified younger age (<50 years), low serum albumin level (<35 g/L), number of previously placed PD catheters, short cuff-exit distance (<2 cm), and S aureus nasal carriage as risk factors for the development of exit-site infections. In conclusion, our study does not show any benefit of the silver ring in preventing catheter-related infections in PD patients. Thus, prevention of infection-related method failure in PD still has to rely on conventional antibiotic treatment strategies and less so on alternative methods.

Clinical laboratory evaluation of the automicrobic system Enterobacteriaceae biochemical card.

The AutoMicrobic System Enterobacteriaceae Biochemical Card (AMS-EBC; Vitek Systems, Inc.) was evaluated in two clinical microbiology laboratories. A total of 502 consecutive clinical isolates representing members of the family Enterobacteriaceae were tested in parallel with the AMS-EBC, API 20E, and Enterotube II systems. Discrepancies between systems were resolved with the conventional methods of Edwards and Ewing (P. R. Edwards and W. H. Ewing [ed.], Identification of Enterobacteriaceae, 1972) and Ewing and Martin (W. H. Ewing and W. J. Martin, in Manual of Clinical Microbiology, 1974) AMS-EBC correctly identified 96.6% and incorrectly identified 3.4% of the isolates. When 12 or more isolates of a species were evaluated, Serratia marcescens, Proteus mirabilis, and Enterobacter cloacae posed the greatest challenge to the systems, with 92.6, 95.2, and 95.3%, respectively, being correctly identified. To confirm the accuracy of identification when all systems agreed, 93 randomly selected isolates were identified by conventional methods. The percent agreement was 100%. The reproducibility of triplicate determinations on 93 randomly selected isolates with the AMS-EBC was 99.6%. The AMS-EBC was found to be an easy, rapid, and accurate method for identification of Enterobacteriaceae.

Rapid isolation of bacteria from septicemic patients by use of an antimicrobial agent removal device.

The new Antimicrobial Removal Device increased the efficacy of conventional methods for isolating bacteria from the blood of septicemic patients. The device removes as much as 100 microgram of antibiotics per ml from whole blood without a significant decrease in bacteria. Of 51 patients studied, 31 yielded positive cultures, and the Antimicrobial Removal Device permitted earlier isolation of the causative agent from blood. Subcultured within the first 12 h yielded 12 positive isolates, as the 31 agents were isolated more rapidly after Antimicrobial Removal Device permitted earlier isolation of the causative agent from blood. Subcultures within the first 12 h yielded 12 positive isolates, as compared to 2 when subcultured without processing in the device. Overall, 21 of the 31 agents were isolated more rapidly after Antimicrobial Removal Device treatment, and four samples were positive only after such treatment. One agent was not isolated in the treated culture.

Comparison of serum and plasma specimens for syphilis serology using the reagin screen test.

One serum and three plasma samples were obtained from each of 125 normal individuals and from 140 patients with treated or untreated syphilis. Serum samples were tested by the Venereal Disease Research Laboratory (VDRL) test and by the Reagin Screen Test (RST). Plasma specimens were tested only with the RST. When tested within 24 h after collection, all specimens from normal individuals were nonreactive. Plasma specimens from normal individuals stored for up to 72 h after collection continued to yield a clearly nonreactive result in 423 of the 426 samples tested by the RST. Serum and plasma samples from syphilis patients tested within 72 h after collection by the RST yielded qualitative and quantitative results almost identical to results of serum tested by the VDRL test.

A single-bottle blood culture system: evaluation and comparison with two other systems.

A commercially available single-bottle blood culture system was evaluated at Ben Taub General Hospital, a Harris County District Hospital. Blood cultures from 1010 patients were examined with the Lederle Diagnostics one-bottle blood culture medium-SPS, Columbia broth (E-Vac, Pfizer), and an in-house-prepared brain heart infusion broth with p-aminobenzoic acid (PABA) and 0.1% agar. Of the 1010 patients examined, blood cultures from 211 (20.8%) were positive, yielding a total of 23 different species of microorganisms. Comparison of the results during clinical evaluation, as well as those from simulated blood cultures, showed that the Lederle Diagnostics blood culture bottle was as effective as the in-house-prepared brain heart infusion and commercially available Columbia broths for isolation of aerobes as well as anaerobes. The techniques used in the evaluation and the advantages of a single-bottle culture system are discussed.