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Tuberculosis (TB) remains an important problem among end-stage renal disease (ESRD) patients. We reviewed the epidemiology of TB and ESRD, investigations of TB exposures in US dialysis facilities, and published guidelines to inform screening and treatment practices among US ESRD patients. Compared to TB in the general population, ESRD patients have 6–25-fold higher TB incidence rates, and mortality during treatment is 2–3-fold higher. Most TB cases among ESRD patients (~90%) occur among non–US-born persons, and an analysis of genotyping data suggests that 80% of all cases result from latent TB infection (LTBI) reactivation. Published TB contact investigations in dialysis facilities have reported cases among ESRD patients and healthcare workers. However, transmission of TB is rare: there were no reports of secondary cases of TB because of exposure to an index-case patient and there were few TB infections, which was demonstrated by low occurrence of newly positive tuberculin skin tests (12%–16%) and conversions (8%–17%) among contacts. Targeted TB education, screening, and treatment for ESRD patients at highest risk for TB exposure (eg, non–US-born persons), using interferon-gamma release assays and short course LTBI regimens (ie, isoniazid-rifapentine weekly for 12 weeks or rifampin daily for 4 months) may be an effective overall strategy for reducing TB burden in ESRD patients.
Tuberculosis (TB) remains an important cause of hospitalization and mortality in the United States. Prevention of TB transmission in acute care facilities relies on prompt identification and implementation of airborne isolation, rapid diagnosis, and treatment of presumptive pulmonary TB patients. In areas with low TB burden, this strategy may result in inefficient utilization of airborne infection isolation rooms (AIIRs). We reviewed TB epidemiology and diagnostic approaches to inform optimal TB detection in low-burden settings. Published clinical prediction rules for individual studies have a sensitivity ranging from 81% to 100% and specificity ranging from 14% to 63% for detection of culture-positive pulmonary TB patients admitted to acute care facilities. Nucleic acid amplification tests (NAATs) have a specificity of >98%, and the sensitivity of NAATs varies by acid-fast bacilli sputum smear status (positive smear, ≥95%; negative smear, 50%–70%). We propose an infection prevention strategy using a clinical prediction rule to identify patients who warrant diagnostic evaluation for TB in an AIIR with an NAAT. Future studies are needed to evaluate whether use of clinical prediction rules and NAATs results in optimized utilization of AIIRs and improved detection and treatment of presumptive pulmonary TB patients.
Infect Control Hosp Epidemiol 2015;36(10):1215–1225
To evaluate national data on healthcare-associated infections (HAIs), device utilization, and antimicrobial resistance in long-term acute care hospitals (LTACHs).
Design and Setting.
Comparison of data from LTACHs and from medical and medical-surgical intensive care units (ICUs) in short-stay acute care hospitals reporting to the National Healthcare Safety Network (NHSN) during 2010.
Rates of central line–associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), and ventilator-associated pneumonia (VAP) as well as device utilization ratios were calculated. For each HAI, pathogen profiles and antimicrobial resistance prevalence were evaluated. Comparisons were made using Poisson regression and the Mood median and x2 tests.
In 2010, 104 LTACHs reported CLABSIs and 57 reported CAUTIs and VAP to the NHSN. Median CLABSI rates in LTACHs (1.25 events per 1,000 device-days reported; range, 0.0-5.96) were comparable to rates in major teaching ICUs and were higher than those in other ICUs. CAUTI rates in LTACHs (median, 2.61; range, 0.0-9.92) were higher and VAP rates (median, 0.0; range, 0.0-3.29) were generally lower than those in ICUs. Central line utilization in LTACHs was higher than that in ICUs, whereas urinary catheter and ventilator utilization was lower. Methicillin resistance among Staphylococcus aureus CLABSIs (83%) and vancomycin resistance among Enterococcus faecalis CAUTIs (44%) were higher in LTACHs than in ICUs. Multidrug resistance among Pseudomonas aeruginosa CAUTIs (25%) was higher in LTACHs than in most ICUs.
CLABSIs and CAUTIs associated with multidrug-resistant organisms present a challenge in LTACHs. Continued HAI surveillance with pathogen-level data can guide prevention efforts in LTACHs.
Infect Control Hosp Epidemiol 2012;33(10):993-1000
To describe a Klebsiella pneumoniae carbapenemase (KPC)–producing carbapenem-resistant Enterobacteriaceae (CRE) outbreak and interventions to prevent transmission.
Design, Setting, and Patients.
Epidemiologic investigation of a CRE outbreak among patients at a long-term acute care hospital (LTACH).
Microbiology records at LTACH A from March 2009 through February 2011 were reviewed to identify CRE transmission cases and cases admitted with CRE. CRE bacteremia episodes were identified during March 2009–July 2011. Biweekly CRE prevalence surveys were conducted during July 2010–July 2011, and interventions to prevent transmission were implemented, including education and auditin? of staff and isolation and cohorting of CRE patients with dedicated nursing staff and shared medical equipment. Trends were evaluated using weighted linear or Poisson regression. CRE transmission cases were included in a case-control study to evaluate risk factors for acquisition. A real-time polymerase chain reaction assay was used to detect the blaKPC gene, and pulsed-field gel electrophoresis was performed to assess the genetic relatedness of isolates.
Ninety-nine CRE transmission cases, 16 admission cases (from 7 acute care hospitals), and 29 CRE bacteremia episodes were identified. Significant reductions were observed in CRE prevalence (49% vs 8%), percentage of patients screened with newly detected CRE (44% vs 0%), and CRE bacteremia episodes (2.5 vs 0.0 per 1,000 patient-days). Cases were more likely to have received β-lactams, have diabetes, and require mechanical ventilation. All tested isolates were KPC-producing K. pneumoniae, and nearly all isolates were genetically related.
CRE transmission can be reduced in LTACHs through surveillance testing and targeted interventions. Sustainable reductions within and across healthcare facilities may require a regional public health approach.
The Czech-born poet, dramatist, essayist and novelist Milan Kundera (b. 1929) is internationally best known for the two once hugely fashionable novels he published after emigrating from Czechoslovakia to France in 1975: The Book of Laughter and Forgetting (BLF, 1979) and The Unbearable Lightness of Being (ULB, 1984). Both are examples of what he calls ‘thinking novels’, in which the plot elements are interpolated with extended authorial reflections on themes often identified in the title of the novel. His novels both reflect and have helped him refine his understanding of the nature and history of the novel, which he expounds in a series of books written originally in French, beginning with The Art of the Novel (AN, 1986). His ideas resonate not so much because of their originality as because of the ‘anti-theoretical’ accessibility of their expression. Drawing above all on the writing of Friedrich Nietzsche (1844–1900) and twentieth-century thinkers influenced by him, including the Russian Formalists, José Ortega y Gasset (1883–1955), Martin Heidegger (1889–1976) and the French existentialists, Kundera sets out a retrospective ‘manifesto’ for the European novel, and attempts in both his fiction and non-fiction to describe and demonstrate an alternative to predictions of its imminent death.
Two ways of being
Throughout his fiction and non-fiction, Kundera suggests that the modern human being responds to existence in two distinct ways. The first response is marked by sentimental egocentrism and is associated with youth, romanticism and the placing of the intellect in the service of the emotions. The human being is consumed by an exhibitionist desire to be acknowledged, but also to belong, to participate in shared experiences, to be one with the shared destiny of humanity, resulting in conformity, homogeneity, mediocrity, superficiality and the ‘stupidity of received ideas’.
To detect an outbreak-related source of Legionella, control the outbreak, and prevent additional Legionella infections from occurring.
Design and Setting.
Epidemiologic investigation of an acute outbreak of hospital-associated Legionnaires disease among outpatients and visitors to a Wisconsin hospital.
Patients with laboratory-confirmed Legionnaires disease who resided in southeastern Wisconsin and had illness onsets during February and March 2010.
Patients with Legionnaires disease were interviewed using a hypothesis-generating questionnaire. On-site investigation included sampling of water and other potential environmental sources for Legionella testing. Case-finding measures included extensive notification of individuals potentially exposed at the hospital and alerts to area healthcare and laboratory personnel.
Laboratory-confirmed Legionnaires disease was diagnosed in 8 patients, all of whom were present at the same hospital during the 10 days prior to their illness onsets. Six patients had known exposure to a water wall-type decorative fountain near the main hospital entrance. Although the decorative fountain underwent routine cleaning and maintenance, high counts of Legionella pneumophila serogroup 1 were isolated from cultures of a foam material found above the fountain trough.
This outbreak of Legionnaires disease was associated with exposure to a decorative fountain located in a hospital public area. Routine cleaning and maintenance of fountains does not eliminate the risk of bacterial contamination. Our findings highlight the need to evaluate the safety of water fountains installed in any area of a healthcare facility.
Initial use of alemtuzumab in multiple sclerosis (MS) was in patients with secondary progressive disease. Just as the efficacy experience of alemtuzumab generated some novel concepts of MS biology, such as the possibility of neuroprotective autoimmunity, so too has exploration of its adverse effects. The most significant adverse effect of alemtuzumab is secondary autoimmunity. A straightforward conclusion from the experience of using alemtuzumab, both open-label and within trials, is that it has the potential to be one of the most efficacious treatments of MS to date. A key lesson from the history of alemtuzumab treatment of MS has been that the disease is only vulnerable to such anti-inflammatory treatments early in its course, before the conditions that predispose to neurodegeneration, and secondary progression, have been set up. The finding of disability improvement after alemtuzumab suggests a new treatment paradigm in MS. There is no signal that alemtuzumab causes neoplasia.
In childhood-onset multiple sclerosis (MS), the cerebrospinal fluid (CSF) profile is not fundamentally different from the adult-onset MS. Magnetic resonance imaging (MRI) is the best imaging technique to detect lesions suggestive of MS in children. The initial clinical course in most patients with childhood-onset MS is relapsing-remitting. In the UCSF cohort, the initial MS event was moderate or severe in 86% of children compared with 56% of adult-onset MS. In the UCSF pediatric-onset cohort, complete recovery was seen in 66%, which was similar to adults seen at the same center, questioning whether children have less irreversible neuronal injury during their first event or/and have a better ability to repair. MS is likely the result of a complex interplay between genes and environment. Potential prognostics factors associated with the assignment of disability milestones have been examined in several cohort studies from adult centers and one cohort from child neurology centers.
In this paper, we report on a method for fabricating an inexpensive microfluidic platform on parchment paper. Parchment paper was selected for this purpose due to its wide availability for culinary applications and hydrophobic silicone-based surface coating. We were able to selectively modify the surface structure and property (hydrophobic to hydrophilic) using a CO2 laser. The modified surface has highly-porous structure which helps to trap chemical and biological reagents for analysis. The treated surface is stable over time and can be used for aqueous droplet assembly. Finally, we demonstrated the applicability of this platform for performing chemical reaction using luminol-based hemoglobin detection.
Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia.
fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 age-matched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object–location paired-associate memory task, with experimental manipulation of mnemonic load.
In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS.
Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis.
African-Caribbean and black African people living in the UK are reported to have a higher incidence of diagnosed psychosis compared with white British people. It has been argued that this may be a consequence of misdiagnosis. If this is true they might be less likely to show the patterns of structural brain abnormalities reported in white British patients. The aim of this study therefore was to investigate whether there are differences in the prevalence of structural brain abnormalities in white and black first-episode psychosis patients.
We obtained dual-echo (proton density/T2-weighted) images from a sample of 75 first-episode psychosis patients and 68 healthy controls. We used high resolution magnetic resonance imaging and voxel-based methods of image analysis. Two separate analyses were conducted: (1) 34 white British patients were compared with 33 white British controls; (2) 41 African-Caribbean and black African patients were compared with 35 African-Caribbean and black African controls.
White British patients and African-Caribbean/black African patients had ventricular enlargement and increased lenticular nucleus volume compared with their respective ethnic controls. The African-Caribbean/black African patients also showed reduced global grey matter and increased lingual gyrus grey-matter volume. The white British patients had no regional or global grey-matter loss compared with their normal ethnic counterparts but showed increased grey matter in the left superior temporal lobe and right parahippocampal gyrus.
We found no evidence in support of our hypothesis. Indeed, the finding of reduced global grey-matter volume in the African-Caribbean/black African patients but not in the white British patients was contrary to our prediction.
Subtle abnormalities in frontal white matter have been reported in
To assess whether impaired integrity of white matter tracts is associated
with bipolar disorder and genetic liability for the disorder.
A total of 19 patients with psychotic bipolar I disorder from multiply
affected families, 21 unaffected first-degree relatives and 18 comparison
individuals (controls) underwent diffusion tensor imaging. Whole brain
voxel-based analyses compared fractional anisotropy between patients and
relatives with controls, and its relationship with a quantitative measure
of genetic liability.
Patients had decreased fractional anisotropy compared with controls in
the genu of the corpus callosum, right inferior longitudinal fasciculus
and left superior longitudinal fasciculus. Increased genetic liability
for bipolar disorder was associated with reduced fractional anisotropy
across distributed regions of white matter in patients and their
Disturbed structural integrity within key intra- and interhemispheric
tracts characterises both bipolar disorder and genetic liability for this
People with prodromal symptoms have a very high risk of developing psychosis.
To use functional magnetic resonance imaging to examine the neurocognitive basis of this vulnerability.
Cross-sectional comparison of regional activation in individuals with an ‘at-risk mental state’ (at-risk group: n=17), patients with first-episode schizophreniform psychosis (psychosis group: n=10) and healthy volunteers (controls: n=15) during an overt verbal fluency task and an N-back working memory task.
A similar pattern of between-group differences in activation was evident across both tasks. Activation in the at-risk group was intermediate relative to that in controls and the psychosis group in the inferior frontal and anterior cingulate cortex during the verbal fluency task and in the inferior frontal, dorsolateral prefrontal and parietal cortex during the N-back task.
The at-risk mental state is associated with abnormalities of regional brain function that are qualitatively similar to, but less severe than, those in patients who have recently presented with psychosis.
Depersonalisation disorder is characterised by emotion suppression, but the cerebral mechanisms of this symptom are not yet fully understood.
To compare brain activation and autonomic responses of individuals with the disorder and healthy controls.
Happy and sad emotion expressions in increasing intensities (neutral to intense) were presented in an implicit event-related functional magnetic resonance imaging (fMRI) design with simultaneous measurement of autonomic responses.
Participants with depersonalisation disorder showed fMRI signal decreases, whereas the control group showed signal increases in response to emotion intensity increases in both happy and sad expressions. The analysis of evoked haemodynamic responses from regions exhibiting functional connectivity between central and autonomic nervous systems indicated that in depersonalisation disorder initial modulations of haemodynamic response occurred significantly earlier (2s post-stimulus) than in the control group (4–6s post-stimulus).
The results suggest that fMRI signal decreases are possible correlates of emotion suppression in depersonalisation disorder.