A near-miss patient incident involving body fluid seeping from a mattress led to a visual inspection of 656 hospital bed mattresses of which 177 were contaminated because of occult damage to mattress covers.
OBJECTIVES: The primary aim of the study was to measure the test characteristics of the National Health Safety Network ventilator-associated event/ventilator-associated condition constructs for detecting ventilator-associated pneumonia. Its secondary aims were to report the clinical features of patients with National Health Safety Network ventilator-associated event/ventilator-associated condition, measure costs of surveillance, and its susceptibility to manipulation.
DESIGN: Prospective cohort study.
SETTING: Two inpatient campuses of an academic medical center.
PATIENTS: Eight thousand four hundred eight mechanically ventilated adults discharged from an ICU.
MEASUREMENTS AND MAIN RESULTS: The National Health Safety Network ventilator-associated event/ventilator-associated condition constructs detected less than a third of ventilator-associated pneumonia cases with a sensitivity of 0.325 and a positive predictive value of 0.07. Most National Health Safety Network ventilator-associated event/ventilator-associated condition cases (93%) did not have ventilator-associated pneumonia or other hospital-acquired complications; 71% met the definition for acute respiratory distress syndrome. Similarly, most patients with National Health Safety Network probable ventilator-associated pneumonia did not have ventilator-associated pneumonia because radiographic criteria were not met. National Health Safety Network ventilator-associated event/ventilator-associated condition rates were reduced 93% by an unsophisticated manipulation of ventilator management protocols.
CONCLUSIONS: The National Health Safety Network ventilator-associated event/ventilator-associated condition constructs failed to detect many patients who had ventilator-associated pneumonia, detected many cases that did not have a hospital complication, and were susceptible to manipulation. National Health Safety Network ventilator-associated event/ventilator-associated condition surveillance did not perform as well as ventilator-associated pneumonia surveillance and had several undesirable characteristics.
Hospital-acquired infections (HAIs) are common in intensive care unit (ICU) patients and are associated with increased morbidity and mortality. There has been an increasing effort to prevent HAIs, and infection control practices are paramount in avoiding these complications. In the last several years, numerous developments have been seen in the infection prevention strategies in various health care settings. This article reviews the modern trends in infection control practices to prevent HAIs in ICUs with a focus on methods for monitoring hand hygiene, updates in isolation precautions, new methods for environmental cleaning, antimicrobial bathing, prevention of ventilator-associated pneumonia, central line-associated bloodstream infections, catheter-associated urinary tract infections, and Clostridium difficile infection.
In a 5-week span during the 1918 influenza A pandemic, more than 2000 patients were admitted to Cook County Hospital in Chicago, with a diagnosis of either influenza or pneumonia; 642 patients, approximately 31% of those admitted, died, with deaths occurring predominantly in patients of age 25 to 30 years. This review summarizes basic information on the biology, epidemiology, control, treatment and prevention of influenza overall, and then addresses the potential impact of pandemic influenza in an intensive care unit setting. Issues that require consideration include workforce staffing and safety, resource management, alternate sites of care surge of patients, altered standards of care, and crisis communication.
OBJECTIVE: To assess the impact of outbreaks of Bordetella pertussis infection on a tertiary care medical system.
DESIGN: Retrospective study.
SETTING: Academic tertiary care medical center and affiliated ambulatory care settings.
SUBJECTS: All patients and healthcare workers (HCWs) who were in close contact with patients with laboratory-confirmed cases of B. pertussis infection from October 1, 2003, through September 30, 2004.
INTERVENTION: Direct and indirect medical center costs were determined, including low and high estimates of time expended in the evaluation and management of exposed patients and HCWs during outbreak investigations of laboratory-confirmed cases of B. pertussis infection.
RESULTS: During this period, 20 primary and 3 secondary laboratory-confirmed cases of B. pertussis infection occurred, with 2 primary pertussis cases and 1 secondary case occurring in HCWs. Outbreak investigations prompted screening of 353 medical center employees. Probable or definitive exposure was identified for 296 HCWs, and 287 subsequently received treatment or prophylaxis for B. pertussis infection. Direct medical center costs for treatment and prophylaxis were $13,416 and costs for personnel time were $19,500-$31,190. Indirect medical center costs for time lost from work were $51,300-$52,300. The total cost of these investigations was estimated to be $85,066-$98,456.
CONCLUSIONS: Frequent B. pertussis exposures had a major impact on our facility. Given the impact of exposures on healthcare institutions, routine vaccination for HCWs may be beneficial.
A cluster of cases of severe influenzal disease was recognized in HIV-infected individuals during the 1997-1998 influenza season. Both primary influenza pneumonia and concomitant viral and bacterial pneumonia were found.
Statistical evaluation of the role of Helicobacter pylori in stress gastritis: applications of splines and bootstrapping to the logistic model
Stress gastritis is a serious problem in the intensive care unit population. The recent discovery of the causal nature of Helicobacter pylori (H. pylori) in the development of gastric ulcers led us to examine its relationship with stress gastritis. We investigated this relationship in 874 veterans admitted to intensive care units who were tested for the presence of H. pylori and followed for 6 weeks for the development of stress gastritis. We fit spline models to assess functional relationships and used the logistic model to determine the association between H. pylori and stress gastritis. The predictive ability of the model was assessed with receiver operating characteristic (ROC) curve analysis and validated with the bootstrapping technique. Increased anti-H. pylori immunoglobulin A concentrations were found to be an important predictor of stress gastritis independent of other known risk factors.
Immunoprophylaxis against klebsiella and pseudomonas aeruginosa infections. The Federal Hyperimmune Immunoglobulin Trial Study Group
To determine if passive immunization could decrease the incidence or severity of Klebsiella and Pseudomonas aeruginosa infections, patients admitted to intensive care units of 16 Department of Veterans Affairs and Department of Defense hospitals were randomized to receive either 100 mg/kg intravenous hyperimmune globulin (IVIG), derived from donors immunized with a 24-valent Klebsiella capsular polysaccharide plus an 8-valent P. aeruginosa O-polysaccharide-toxin A conjugate vaccine, or an albumin placebo. The overall incidence and severity of vaccine-specific Klebsiella plus Pseudomonas infections were not significantly different between the groups receiving albumin and IVIG. There was some evidence that IVIG may decrease the incidence (2.7% albumin vs. 1.2% IVIG) and severity (1.0% vs. 0.3%) of vaccine-specific Klebsiella infections, but these reductions were not statistically significant. The trial was stopped because it was statistically unlikely that IVIG would be protective against Pseudomonas infections at the dosage being used. Patients receiving IVIG had more adverse reactions (14.4% vs. 9.2%).
Risk factors for upper gastrointestinal bleeding in intensive care unit patients: role of helicobacter pylori. Federal Hyperimmune Immunoglobulin Therapy Study Group
OBJECTIVE: To determine the role of preexisting Helicobacter pylori infection in the development of acute upper gastrointestinal (GI) hemorrhage in intensive care unit (ICU) patients in relation to other potential predisposing risk factors.
DESIGN: Prospective, multicenter, cohort study.
SETTING: Medical and surgical ICUs in six tertiary care Department of Veterans Affairs Medical Centers.
PATIENTS: Eight-hundred seventy-four patients without previous GI bleeding or peptic ulcer disease who were enrolled in a multicenter, randomized, controlled trial of prophylactic intravenous immunoglobulin to prevent ICU-associated infections.
INTERVENTIONS: This substudy of the larger intravenous immunoglobulin study only involved data analysis and had no intervention. All patients were enrolled in the larger study where they received intravenous immunoglobulin or placebo as intervention.
MEASUREMENTS AND MAIN RESULTS: Patients were prospectively evaluated for the development of acute upper GI hemorrhage while in an ICU. Anti-H. pylori immunoglobulin G and immnoglobulin A concentrations were determined by enzyme immunoassay on preintervention serum samples. Seventy-six (9%) patients had over upper GI bleeding and a mortality rate of 49%, as compared with a 15% mortality rate in patients who did not bleed (p < .001). By logistic regression analysis, the following factors were associated with an increased risk of bleeding: acute hepatic failure, prolonged duration of nasogastric tube placement, alcoholism, and an increased serum concentration of anti-H. pylori immunoglobulin A.
CONCLUSIONS: Increased anti-H. pylori immunoglobulin A concentrations, prolonged nasogastric intubation, alcoholism, and acute hepatic failure were found to be independently correlated with the development of acute GI bleeding in an ICU setting. These observations should be prospectively confirmed in an independent population before being used for treatment guidelines.
Although the antimicrobial activity of lactoferrin has been well described, its mechanism of action has been poorly characterized. Recent work has indicated that in addition to binding iron, human lactoferrin damages the outer membrane of gram-negative bacteria. In this study, we determined whether bovine lactoferrin and a pepsin-derived bovine lactoferrin peptide (lactoferricin) fragment have similar activities. We found that both 20 microM bovine lactoferrin and 20 microM lactoferricin release intrinsically labeled [3H]lipopolysaccharide ([3H]LPS) from three bacterial strains, Escherichia coli CL99 1-2, Salmonella typhimurium SL696, and Salmonella montevideo SL5222. Under most conditions, more LPS is released by the peptide fragment than by whole bovine lactoferrin. In the presence of either lactoferrin or lactoferricin there is increased killing of E. coli CL99 1-2 by lysozyme. Like human lactoferrin, bovine lactoferrin and lactoferricin have the ability to bind to free intrinsically labeled [3H]LPS molecules. In addition to these effects, whereas bovine lactoferrin was at most bacteriostatic, lactoferricin demonstrated consistent bactericidal activity against gram-negative bacteria. This bactericidal effect is modulated by the cations Ca2+, Mg2+, and Fe3+ but is independent of the osmolarity of the medium. Transmission electron microscopy of bacterial cells exposed to lactoferricin show the immediate development of electron-dense "membrane blisters." These experiments offer evidence that bovine lactoferrin and lactoferricin damage the outer membrane of gram-negative bacteria. Moreover, the peptide fragment lactoferricin has direct bactericidal activity. As lactoferrin is exposed to proteolytic factors in vivo which could cleave the lactoferricin fragment, the effects of this peptide are of both mechanistic and physiologic relevance.
This is the December 2015 issue of the UMass Center for Clinical and Translational Science Newsletter containing news and events of interest.
Gonorrhea is a highly prevalent disease resulting in significant morbidity worldwide, with an estimated 106 cases reported annually. Neisseria gonorrhoeae, the causative agent of gonorrhea, colonizes and infects the human genital tract and often evades host immune mechanisms until successful antibiotic treatment is used. The alarming increase in antibiotic-resistant strains of N. gonorrhoeae, the often asymptomatic nature of this disease in women and the lack of a vaccine directed at crucial virulence determinants have prompted us to perform transcriptome analysis to understand gonococcal gene expression patterns during natural infection. We sequenced RNA extracted from cervico-vaginal lavage samples collected from women recently exposed to infected male partners and determined the complete N. gonorrhoeae transcriptome during infection of the lower genital tract in women. On average, 3.19% of total RNA isolated from female samples aligned to the N. gonorrhoeae NCCP11945 genome and 1750 gonococcal ORFs (65% of all protein-coding genes) were transcribed. High expression in vivo was observed in genes encoding antimicrobial efflux pumps, iron response, phage production, pilin structure, outer membrane structures and hypothetical proteins. A parallel analysis was performed using the same strains grown in vitro in a chemically defined media (CDM). A total of 140 genes were increased in expression during natural infection compared to growth in CDM, and 165 genes were decreased in expression. Large differences were found in gene expression profiles under each condition, particularly with genes involved in DNA and RNA processing, iron, transposase, pilin and lipoproteins. We specifically interrogated genes encoding DNA binding regulators and iron-scavenging proteins, and identified increased expression of several iron-regulated genes, including tbpAB and fbpAB, during infection in women as compared to growth in vitro, suggesting that during infection of the genital tract in women, the gonococcus is exposed to an iron deplete environment. Collectively, we demonstrate that a large portion of the gonococcal genome is expressed and regulated during mucosal infection including genes involved in regulatory functions and iron scavenging.
Knowledge on HPV Vaccine and Cervical Cancer Facilitates Vaccine Acceptability among School Teachers in Kitui County, Kenya
BACKGROUND: Vaccines against human papillomavirus (HPV) infection have the potential to reduce the burden of cervical cancer. School-based delivery of HPV vaccines is cost-effective and successful uptake depends on school teachers' knowledge and acceptability of the vaccine. The aim of this study is to assess primary school teachers' knowledge and acceptability of HPV vaccine and to explore facilitators and barriers of an ongoing Gavi Alliance-supported vaccination program in Kitui County, Kenya.
METHODS: This was a cross-sectional, mixed methods study in Central Division of Kitui County where the Ministry of Health is offering the quadrivalent HPV vaccine to grade four girls. Data on primary school teachers' awareness, knowledge and acceptability of HPV vaccine as well as facilitators and barriers to the project was collected through self-administered questionnaires and two focus group discussions.
RESULTS: 339 teachers (60% female) completed the survey (62% response rate) and 13 participated in 2 focus group discussions. Vaccine awareness among teachers was high (90%), the level of knowledge about HPV and cervical cancer among teachers was moderate (48%, SD = 10.9) and females scored higher than males (50% vs. 46%, p = 0.002). Most teachers (89%) would recommend the vaccine to their daughter or close relatives. Those who would recommend the vaccine had more knowledge than those who would not (p = < 0.001). The main barriers were insufficient information about the vaccine, poor accessibility of schools, absenteeism of girls on vaccine days, and fear of side effects.
CONCLUSIONS: Despite low to moderate levels of knowledge about HPV vaccine among school teachers, vaccine acceptability is high. Teachers with little knowledge on HPV vaccine are less likely to accept the vaccine than those who know more; this may affect uptake if not addressed. Empowering teachers to be vaccine champions in their community may be a feasible way of disseminating information about HPV vaccine and cervical cancer.
Activation-induced cytidine deaminase (AID) is essential for class switch recombination (CSR) and somatic hypermutation (SHM) of Ig genes. The C terminus of AID is required for CSR but not for SHM, but the reason for this is not entirely clear. By retroviral transduction of mutant AID proteins into aid-/- mouse splenic B cells, we show that 4 amino acids within the C terminus of mouse AID, when individually mutated to specific amino acids (R190K, A192K, L196S, F198S), reduce CSR about as much or more than deletion of the entire C terminal 10 amino acids. Similar to DeltaAID, the substitutions reduce binding of UNG to Ig Smu regions and some reduce binding of Msh2, both of which are important for introducing S region DNA breaks. Junctions between the IgH donor switch (S)mu and acceptor Salpha regions from cells expressing DeltaAID or the L196S mutant show increased microhomology compared to junctions in cells expressing wild-type AID, consistent with problems during CSR and the use of alternative end-joining, rather than non-homologous end-joining (NHEJ). Unlike deletion of the AID C terminus, 3 of the substitution mutants reduce DNA double-strand breaks (DSBs) detected within the Smu region in splenic B cells undergoing CSR. Cells expressing these 3 substitution mutants also have greatly reduced mutations within unrearranged Smu regions, and they decrease with time after activation. These results might be explained by increased error-free repair, but as the C terminus has been shown to be important for recruitment of NHEJ proteins, this appears unlikely. We hypothesize that Smu DNA breaks in cells expressing these C terminus substitution mutants are poorly repaired, resulting in destruction of Smu segments that are deaminated by these mutants. This could explain why these mutants cannot undergo CSR.
In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs) on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices.
A Social-Ecological View of Barriers and Facilitators for HIV Treatment Adherence: Interviews with Puerto Rican HIV Patients
PURPOSE: To identify perceived barriers and facilitators for HAART adherence among people living with HIV/AIDS in Southern Puerto Rico using a Social Ecological framework.
PATIENTS AND METHODS: Individual in-depths interviews were conducted with 12 HIV patients with a history of HAART non-adherence. Interviews were audio-taped and transcribed. Content analysis was performed for each transcribed interview by three independent coders using a codebook. Using Atlas TI, super-codes and families were generated to facilitate the categorization tree as well as grounded analyses and density estimates.
RESULTS: Most participants reported a monthly income of $500 or less (n = 7), a high school education level (n = 7), being unemployed (n = 9) and being recipients of government health insurance (n = 11). Three out of six women reported living alone with their children and most men informed living with their parents or other relatives (n = 4). For the grounded analyses, the top four sub-categories linked to high number of quotations were mental health barriers (G = 32) followed by treatment regimen (G = 28), health system (G = 24) and interpersonal relations (G = 16). The top four sub-categories linked to high number of codes are treatment regimen (D = 4), health status perception (D = 3), interpersonal relations (D = 3) and health system (D = 3).
CONCLUSION: The results of this study suggest the interconnection of HIV treatment adherence barriers at various system levels. Future studies on HIV treatment barriers should explore these interactions and investigate the possible synergistic effect on non-adherent behavior.
This study sought to characterize the experience of stress, treatment patterns, and medical and disability profile in the migraineur population to better understand how the experience of migraines impacts the social and psychological functioning of this group. A 30-minute self-report survey was presented via a migraine-specific website with data collection occurring between May 15 and June 15, 2012. Recruitment for the study was done through online advertisements. In total, 2,907 individuals began the survey and 2,735 met the inclusion criteria for the study. The sample was predominantly female (92.8%). Migraine-associated stress was correlated with length of time since first onset of symptoms (P < 0.01) and number of symptoms per month (P < 0.01). Disorders related to stress, such as depression (P < 0.01) and anxiety (P < 0.01), were also positively correlated with the measured stress resulting from migraines. Migraine-associated stress must be understood as a multidimensional experience with broader impacts of stress on an individual correlating much more highly with negative mental and physical health profiles. Stress resulting from frequent migraine headaches may contribute to the development of medical and psychological comorbidities and may be a part of a cyclical relationship wherein stress is both a cause and effect of the social and medical impairments brought about by migraine.
Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium
Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.
Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined.
Rearrest has been predicted by hemodynamic activity in the anterior cingulate cortex (ACC) during error-processing (Aharoni et al., 2013). Here, we evaluate the predictive power after adding an additional imaging modality in a subsample of 45 incarcerated males from Aharoni et al. (2013). Event-related potentials (ERPs) and hemodynamic activity were collected during a Go/NoGo response inhibition task. Neural measures of error-processing were obtained from the ACC and two ERP components, the error-related negativity (ERN/Ne) and the error positivity (Pe). Measures from the Pe and ACC differentiated individuals who were and were not subsequently rearrested. Cox regression, logistic regression, and support vector machine (SVM) neuroprediction models were calculated. Each of these models proved successful in predicting rearrest and SVM provided the strongest results. Multimodal neuroprediction SVM models with out of sample cross-validating accurately predicted rearrest (83.33%). Offenders with increased Pe amplitude and decreased ACC activation, suggesting abnormal error-processing, were at greatest risk of rearrest.