Incidence of Pseudomonas aeruginosa bacteremia: a population-based study

Background

The incidence of Pseudomonas aeruginosa bacteremia has not been defined in a population-based investigation.

Methods

We performed a retrospective, population-based incidence study using resources of the Rochester Epidemiology Project of Olmsted County, Minnesota. We identified all Olmsted County residents with P. aeruginosa bacteremia between January 1, 1997, and December 31, 2006, by microbiology records in the only 2 laboratories in the county. Medical records were reviewed to confirm diagnosis, residency status, and clinical characteristics.

Results

Age-adjusted incidence per 100,000 person-years was 10.8 (95% confidence interval [CI], 7.5-14.0) in men and 3.7 (95% CI, 2.2-5.2) in women for total P. aeruginosa bacteremia, and 8.4 (95% CI, 5.5-11.2) in men and 2.5 (95% CI, 1.3-3.8) in women for monomicrobial P. aeruginosa bacteremia. There was no significant change in incidence of total P. aeruginosa bacteremia during the past decade (P = .418). Incidence increased exponentially with age, with a greater magnitude of increase in men compared with women for total and monomicrobial P. aeruginosa bacteremia (P = .007 and P = .015, respectively). In patients with monomicrobial P. aeruginosa bacteremia, the median age was 69 years, and 78.4% of cases were either nosocomial or health care associated. Most patients had multiple comorbid conditions. The urinary tract was the most common primary source of infection. The 28-day all-cause mortality of monomicrobial P. aeruginosa bacteremia was 25.5%. In vitro susceptibility to ciprofloxacin was 95.3%.

Conclusion

To our knowledge, this is the first population-based incidence study of P. aeruginosa bacteremia. The incidence of P. aeruginosa bacteremia has remained stable during the past decade. Fluoroquinolone susceptibility is high among local P. aeruginosa bacteremia isolates.     

System Strategies for Colorectal Cancer Screening at Federally Qualified Health Centers

Objectives. We assessed the protocols and system processes for colorectal cancer (CRC) screening at federally qualified health centers (FQHCs) in 4 midwestern states.Methods. We identified 49 FQHCs in 4 states. In January 2013, we mailed their medical directors a 49-item questionnaire about policies on CRC screening, use of electronic medical records, types of CRC screening recommended, clinic tracking systems, referrals for colonoscopy, and barriers to providing CRC.Results. Forty-four questionnaires (90%) were returned. Thirty-three of the respondents (75%) estimated the proportion of their patients up-to-date with CRC screening, with a mean of 35%. One major barrier to screening was inability to provide colonoscopy for patients with a positive fecal occult blood test (59%). The correlation of system strategies and estimated percentage of patients up-to-date with CRC screening was 0.43 (P = .01).Conclusions. CRC system strategies were associated with higher CRC screening rates. Implementing system strategies for CRC screening takes time and effort and is important to maintain, to help prevent, or to cure many cases of CRC, the second leading cause of cancer in the United States.Federally qualified health centers (FQHCs) attempt to provide comprehensive, quality primary health care services to medically underserved communities and vulnerable populations. Approximately 1198 centers receive operating grants from the Public Health Service Act and thus qualify for reimbursement from Medicare and Medicaid.1 FQHCs served 21 million patients in 2012, of whom 36% were uninsured and 92% were living below the 200% poverty level.1 One of the services provided by FQHCs is colorectal cancer (CRC) screening through stool testing for occult blood.2 This service is covered under the Medicare FQHC benefit for persons aged 65 years and older and for those who qualify for the Medicaid program.3CRC is the second leading cause of cancer deaths in the United States.4 Only 63% of US adults report being up-to-date with CRC screening.5 CRC is a disease that is largely preventable; colonoscopy, through detection of early tumors and removal of precancerous polyps, could prevent 65% of CRC cases.6,7 Several national organizations have guidelines for CRC screening.8,9 National guidelines promote any of several tests for CRC screening: tests that pick up occult bleeding and endoscopic tests that visualize all or part of the colon.8–10Clinical tests to directly visualize colorectal cancer and precancerous polyps are colonoscopy, flexible sigmoidoscopy, double-contrast barium enema, and computed tomographic colonography (virtual colonoscopy). Fecal occult blood tests (FOBTs), which detect blood in the stool that is not visible and that indicates possible cancer, are the guaiac-based test and the fecal immunochemical test (FIT). FOBTs are recommended annually, and colonoscopy is recommended every 10 years, if no polyps are found.8–10 FOBTs are much less expensive than colonoscopy and are often preferred by patients. In many safety net settings, FOBTs are the initial option for patients, because of the prohibitive cost and limited availability of colonoscopy.11,12Through an infrastructure grant to enhance community-based cancer control in Iowa, we visited 4 FQHCs in Iowa and learned that FOBTs were available for use, but were for the most part not given to patients to avoid having to arrange and pay for a follow-up colonoscopy if FOBT results were positive. One FQHC director explained that the annual budget included a fund for extra tests that might be needed for any medical reason, and once these funds were exhausted, no more funding was available in that year. Thus, CRC screening was not a top priority, because of many other competing health care needs.To enhance CRC screening, system strategies are appropriate. A system strategy is a group of interrelated items that are part of a plan of action to accomplish a specific goal, such as improving CRC screening. Many different system strategies have been identified for improving CRC screening, such as physician recommendation,13,14 mailed patient reminders,15–17 and electronic medical record (EMR) physician reminders.18,19Patients at greatest risk for not receiving CRC screening are racial and ethnic minorities, Asians and Hispanics, and individuals who lack a usual source of health care or health insurance.20 Underuse of CRC screening is frequently associated with socioeconomic disadvantage21 and is associated with higher late-stage CRC rates.22 Because many of our nation’s most disadvantaged individuals make use of FQHCs, we assessed the protocols and system processes in place for CRC screening at FQHCs in 4 midwestern states and estimated rates of CRC screening in these FQHCs.     

Substance use disorders and Cluster B personality disorders: physiological, cognitive, and environmental correlates in a college sample

Substance use disorders (SUDs) and Cluster B personality disorders (PDs) are both marked by impulsivity and poor behavioral control and may result in part from shared neurobiological or executive cognitive functioning deficits. To examine the potential utility of such models in explaining variance in SUDs and PDs at the lower end of symptom expression and impairment, 123 (73 female) volunteer college students were administered 2 measures of executive cognitive functioning; a task assessing autonomic reactivity to aversive noise blasts; a life events and a peer substance use measure; and structured clinical interviews to assess symptoms of substance abuse/dependence and antisocial, borderline, histrionic, and narcissistic PDs. As expected, symptoms of SUDs and PDs were significantly positively correlated. Antisocial PD, alcohol and cannabis use disorder symptoms were significantly positively related to proportion of friends who use alcohol and drugs regularly and drug use among romantic partners. Number of negative life events was positively related to PD symptoms and to alcohol use disorder symptoms. Executive cognitive functioning was not related to SUD and PD symptoms in the expected direction. Findings suggest that, among higher functioning young adults, environmental factors may be particularly relevant to our understanding of SUDs and certain PDs.     

Analysis of the premalignant stages of Barrett's oesophagus through to adenocarcinoma by comparative genomic hybridization

OBJECTIVES: Barrett's oesophagus is a pre-neoplastic lesion, which develops as a complication of chronic gastro-oesophageal reflux disease and predisposes the patient to oesophageal adenocarcinoma. Our aim was to characterize karyotypic changes that may occur during the progression of Barrett's metaplasia through low-grade dysplasia and high-grade dysplasia to adenocarcinoma. METHODS: The technique of comparative genomic hybridization was used to characterize genome-wide changes in biopsies from patients with low-grade dysplasia, low-grade dysplasia plus high-grade dysplasia, high-grade dysplasia or adenocarcinoma. Both fresh and archival material was examined. RESULTS: Comparative genomic hybridization revealed a large amount of widespread chromosome instability at the high-grade dysplasia stage. No significant chromosome changes were detectable by comparative genomic hybridization in patients with low-grade dysplasia. Karyotypic changes in the adenocarcinoma patients were more specific than those found in the high-grade dysplasia patients. Chromosome 4 was amplified most often in high-grade dysplasia and chromosome 8q was amplified most frequently in the adenocarcinomas. CONCLUSIONS: These data demonstrate that high-grade dysplasia is the stage exhibiting widespread chromosome instability, which is detectable by comparative genomic hybridization. This instability is undetectable in low-grade dysplasia. The chromosome variation seen at high-grade dysplasia may be the source of more specific karyotypes that progress to adenocarcinoma. Importantly, we have identified chromosome 4 amplification as being heavily involved in the initiation of Barrett's progression. Specific chromosome changes (4 and 8q) may represent important regions on which to focus attention in future studies, with a view to identifying diagnostic markers.     

Trefoil factor 3 in perinatal pancreas is increased by gestational low protein diet and associated with accelerated β-cell maturation

The endocrine pancreas expands markedly in the first postnatal days and the insulin producing β-cells initiate a functional maturation preceded by a morphological change of the islets of Langerhans. Trefoil factor 3 (TFF3) is a secreted peptide expressed in intestinal epithelia, where it promotes migration, but its role in the pancreas is not characterized. The aim of this study was to examine the expression and function of TFF3 in perinatal rat pancreas, ex vivo cultured fetal rat pancreas and in the rat β-cell line INS-1E.

Control or gestational low-protein diet perinatal rat pancreas was harvested at embryonic day 20 (E20), day of birth (P0) and postnatal day 2 (P2). TFF3 mRNA was upregulated 4.5-fold at P0 vs. E20 and downregulated again at P2. In protein-undernourished pups induction of TFF3 at P0 was further increased to 9.7-fold and was increased at P2. TFF3 caused tyrosine phosphorylation of EGFR in INS-1E β-cells, and purified recombinant TFF3 increased both attachment and spreading of INS-1E β-cells. In ex vivo cultures of collagenase digested fetal rat pancreas, a model of perinatal β-cell maturation, TFF3 increased cellular spreading as well as insulin mRNA levels. TFF3 also increased the expression of Pref1/Dlk1 that shares similarities in expression and regulation with TFF3.

These results suggest that TFF3 may promote adhesion and spreading of cells to accelerate β-cell maturation. This study indicates a functional role for TFF3 in pancreatic β-cell maturation in the perinatal period, which is altered by low protein diet during gestation.     

Fibroblastic foci in usual interstitial pneumonia: idiopathic versus collagen vascular disease

A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies from 108 patients with usual interstitial pneumonia (nine with collagen vascular disease) and assigned a score (absent 0, mild 1, moderate 2, and marked 3) for fibroblastic foci. Patients with idiopathic usual interstitial pneumonia had a higher median profusion of fibroblastic foci (1.75 vs. 1.0, p = 0.003). Baseline characteristics were similar, although patients with a collagen vascular disease were younger, had a shorter duration of symptoms, and had a higher percentage of predicted total lung capacity. Profusion of fibroblastic foci was the most discriminative feature for separating idiopathic from collagen vascular disease-associated usual interstitial pneumonia (odds ratio 8.31; 95% confidence interval, 1.98, 59.42; p = 0.002 for a one-unit increase in fibroblastic foci score). No deaths were noted in the collagen vascular disease-associated usual interstitial pneumonia group; 52 deaths occurred in the idiopathic usual interstitial pneumonia group (log rank; p = 0.005). We conclude that patients with collagen vascular disease-associated usual interstitial pneumonia have fewer fibroblastic foci and improved survival.     

Using Vascular Closure Devices Following Out-Of-Hospital Cardiac Arrest?

Objectives and Background: Despite a generally broad use of vascular closure devices (VCDs), it remains unclear whether they can also be used in victims from out-of-hospital cardiac arrest (OHCA) treated with mild therapeutic hypothermia (MTH).Methods: All victims from OHCA who received immediate coronary angiography after OHCA between January 1^st 2008 and December 31^st 2013 were included in this study. The operator decided to either use a VCD (Angio-Seal™) or manual compression for femoral artery puncture. The decision to induce MTH was based on the clinical circumstances.Results: 76 patients were included in this study, 46 (60.5%) men and 30 (39.5%) women with a mean age of 64.2 ± 12.8 years. VCDs were used in 26 patients (34.2%), and 48 patients (63.2%) were treated with MTH. While there were significantly more overall vascular complications in the group of patients treated with MTH (12.5% versus 0.0%; p=0.05), vascular complications were similar between patients with VCD or manual compression, regardless of whether or not they were treated with MTH.Conclusion: In our study, the overall rate of vascular complications related to coronary angiography was higher in patients treated with mild therapeutic hypothermia, but was not affected by the application of a vascular closure device. Therefore, our data suggest that the use of VCDs in victims from OHCA might be feasible and safe in patients treated with MTH as well, at least if the decision to use them is individually carefully determined.     

Anti-IL-7 receptor-α reverses established type 1 diabetes in nonobese diabetic mice by modulating effector T-cell function

Genetic variation in the IL-7 receptor-α (IL-7R) gene is associated with susceptibility to human type 1 diabetes (T1D). Here we investigate the therapeutic efficacy and mechanism of IL-7Rα antibody in a mouse model of T1D. IL-7Rα antibody induces durable, complete remission in newly onset diabetic mice after only two to three injections. IL-7 increases, whereas IL-7Rα antibody therapy reduces, the IFN-γ-producing CD4(+) (T(H)1) and IFN-γ-producing CD8(+) T cells. Conversely, IL-7 decreases and IL-7Rα antibody enhances the inhibitory receptor Programmed Death 1 (PD-1) expression in the effector T cells. Programmed Death 1 blockade reversed the immune tolerance mediated by the IL-7Rα antibody therapy. Furthermore, IL-7Rα antibody therapy increases the frequency of regulatory T cells without affecting their suppressor activity. The durable efficacy and the multipronged tolerogenic mechanisms of IL-7Rα antibody therapy suggest a unique disease-modifying approach to T1D.