Congenital Cytomegalovirus Mortality in the United States, 1990–2006

Cytomegalovirus (CMV) is a member of the herpes family of viruses, which is transmitted by sexual and non-sexual contact. Human CMV causes a wide variety of infection and illness in healthy adults, in those with compromised immune systems (such as AIDS), in those with cardiovascular disease, and in pregnant women who can pass the infection to their unborn child (congenital CMV). Treatment options for congenital CMV are limited and no effective vaccine to protect against CMV currently exists. Previous studies have demonstrated that African Americans and Mexican Americans are at an increased risk for congenital CMV infections. In this study, the authors examined death certificate data of US Residents from 1990–2006 in which congenital CMV was listed as one of the diagnoses at death. The analysis demonstrated that there is a significant burden of congenital CMV deaths in infants (<1 year old) with African Americans and Native Americans overrepresented. This study helps quantify congenital CMV deaths among US residents and adds further support to the importance of funding CMV vaccine research

Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.

Abstract Introduction Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI). Methods Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings. Results We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year. Conclusions In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship

Skin and soft tissue infections in hospitalized and critically ill patients: a nationwide population-based study

<p>Abstract</p> <p>Background</p> <p>The proportional distributions of various skin and soft tissue infections (SSTIs) with/without intensive care are unclear. Among SSTI patients, the prevalence and significance of complicating factors, such as comorbidities and infections other than skin/soft tissue (non-SST infections), remain poorly understood. We conducted this population-based study to characterize hospitalized SSTI patients with/without intensive care and to identify factors associated with patient outcome.</p> <p>Methods</p> <p>We analyzed first-episode SSTIs between January 1, 2005 and December 31, 2007 from the hospitalized claims data of a nationally representative sample of 1,000,000 people, about 5% of the population, enrolled in the Taiwan National Health Insurance program. We classified 18 groups of SSTIs into three major categories: 1) superficial; 2) deeper or healthcare-associated; and 3) gangrenous or necrotizing infections. Multivariate logistic regression models were applied to identify factors associated with intensive care unit (ICU) admission and hospital mortality.</p> <p>Results</p> <p>Of 146,686 patients ever hospitalized during the 3-year study period, we identified 11,390 (7.7%) patients having 12,030 SSTIs. Among these SSTI patients, 1,033 (9.1%) had ICU admission and 306 (2.7%) died at hospital discharge. The most common categories of SSTIs in ICU and non-ICU patients were "deeper or healthcare-associated" (62%) and "superficial" (60%) infections, respectively. Of all SSTI patients, 45.3% had comorbidities and 31.3% had non-SST infections. In the multivariate analyses adjusting for demographics and hospital levels, the presence of several comorbid conditions was associated with ICU admission or hospital mortality, but the results were inconsistent across most common SSTIs. In the same analyses, the presence of non-SST infections was consistently associated with increased risk of ICU admission (adjusted odds ratios [OR] 3.34, 95% confidence interval [CI] 2.91-3.83) and hospital mortality (adjusted OR 5.93, 95% CI 4.57-7.71).</p> <p>Conclusions</p> <p>The proportional distributions of various SSTIs differed between ICU and non-ICU patients. Nearly one-third of hospitalized SSTI patients had non-SST infections, and the presence of which predicted ICU admission and hospital mortality.</p

The association between histamine 2 receptor antagonist use and Clostridium difficile infection: a systematic review and meta-analysis.

Background Clostridium difficile infection (CDI) is a major health problem. Epidemiological evidence suggests that there is an association between acid suppression therapy and development of CDI. Purpose We sought to systematically review the literature that examined the association between histamine 2 receptor antagonists (H2RAs) and CDI. Data source We searched Medline, Current Contents, Embase, ISI Web of Science and Elsevier Scopus from 1990 to 2012 for all analytical studies that examined the association between H2RAs and CDI. Study selection Two authors independently reviewed the studies for eligibility. Data extraction Data about studies characteristics, adjusted effect estimates and quality were extracted. Data synthesis Thirty-five observations from 33 eligible studies that included 201834 participants were analyzed. Studies were performed in 6 countries and nine of them were multicenter. Most studies did not specify the type or duration of H2RAs therapy. The pooled effect estimate was 1.44, 95% CI (1.22–1.7), I2 = 70.5%. This association was consistent across different subgroups (by study design and country) and there was no evidence of publication bias. The pooled effect estimate for high quality studies was 1.39 (1.15–1.68), I2 = 72.3%. Meta-regression analysis of 10 study-level variables did not identify sources of heterogeneity. In a speculative analysis, the number needed to harm (NNH) with H2RAs at 14 days after hospital admission in patients receiving antibiotics or not was 58, 95% CI (37, 115) and 425, 95% CI (267, 848), respectively. For the general population, the NNH at 1 year was 4549, 95% CI (2860, 9097). Conclusion In this rigorous systematic review and meta-analysis, we observed an association between H2RAs and CDI. The absolute risk of CDI associated with H2RAs is highest in hospitalized patients receiving antibiotics

Merkel cell carcinoma: a population-based study on mortality and the association with other cancers

Few population-based epidemiological data are available on Merkel cell carcinoma (MCC), a rare lethal non-melanoma skin cancer. We analysed multiple-cause-of-death records to describe MCC mortality and trends and the association with other primary cancers. We reviewed all 6,713,059 death certificates in Italy (1995-2006) to identify those mentioning MCC. We evaluated the association with other primary cancers by calculating the ratio of observed to expected deaths, using a standardized mortality ratio (SMR)-like analysis. We also evaluated the geographic distribution of deaths. We identified 351 death certificates with the mention of MCC. The age-adjusted mortality was 0.031/100,000, with a significant trend of increase and a slight north-south gradient. There was a significant deficit for solid cancers (SMR = 0.15) and a non-significant excess for lymphohematopoietic malignancies (SMR = 1.62). There were significant excesses for chronic lymphocytic leukemia (SMR = 4.07) and Waldenstrom's macroglobulinemia (SMR = 27.2) and a non-significant excess for chronic myeloid leukemia (SMR = 5.12). The increase in MCC mortality reflects the incidence trend in the literature. The association with chronic lymphocytic leukemia confirms the importance of immunologic factors in MCC. Regarding Waldenstrom's macroglobulinemia, an association with MCC has never been reported

Comparative genomic analysis of toxin-negative strains of Clostridium difficile from humans and animals with symptoms of gastrointestinal disease

Background: Clostridium difficile infections (CDI) are a significant health problem to humans and food animals. Clostridial toxins ToxA and ToxB encoded by genes tcdA and tcdB are located on a pathogenicity locus known as the PaLoc and are the major virulence factors of C. difficile. While toxin-negative strains of C. difficile are often isolated from faeces of animals and patients suffering from CDI, they are not considered to play a role in disease. Toxin-negative strains of C. difficile have been used successfully to treat recurring CDI but their propensity to acquire the PaLoc via lateral gene transfer and express clinically relevant levels of toxins has reinforced the need to characterise them genetically. In addition, further studies that examine the pathogenic potential of toxin-negative strains of C. difficile and the frequency by which toxin-negative strains may acquire the PaLoc are needed. Results: We undertook a comparative genomic analysis of five Australian toxin-negative isolates of C. difficile that lack tcdA, tcdB and both binary toxin genes cdtA and cdtB that were recovered from humans and farm animals with symptoms of gastrointestinal disease. Our analyses show that the five C. difficile isolates cluster closely with virulent toxigenic strains of C. difficile belonging to the same sequence type (ST) and have virulence gene profiles akin to those in toxigenic strains. Furthermore, phage acquisition appears to have played a key role in the evolution of C. difficile. Conclusions: Our results are consistent with the C. difficile global population structure comprising six clades each containing both toxin-positive and toxin-negative strains. Our data also suggests that toxin-negative strains of C. difficile encode a repertoire of putative virulence factors that are similar to those found in toxigenic strains of C. difficile, raising the possibility that acquisition of PaLoc by toxin-negative strains poses a threat to human health. Studies in appropriate animal models are needed to examine the pathogenic potential of toxin-negative strains of C. difficile and to determine the frequency by which toxin-negative strains may acquire the PaLoc

Genome Mining for Radical SAM Protein Determinants Reveals Multiple Sactibiotic-Like Gene Clusters

Thuricin CD is a two-component bacteriocin produced by Bacillus thuringiensis that kills a wide range of clinically significant Clostridium difficile. This bacteriocin has recently been characterized and consists of two distinct peptides, Trnβ and Trnα, which both possess 3 intrapeptide sulphur to α-carbon bridges and act synergistically. Indeed, thuricin CD and subtilosin A are the only antimicrobials known to possess these unusual structures and are known as the sactibiotics (sulplur to alpha carbon-containing antibiotics). Analysis of the thuricin CD-associated gene cluster revealed the presence of genes encoding two highly unusual SAM proteins (TrnC and TrnD) which are proposed to be responsible for these unusual post-translational modifications. On the basis of the frequently high conservation among enzymes responsible for the post-translational modification of specific antimicrobials, we performed an in silico screen for novel thuricin CD–like gene clusters using the TrnC and TrnD radical SAM proteins as driver sequences to perform an initial homology search against the complete non-redundant database. Fifteen novel thuricin CD–like gene clusters were identified, based on the presence of TrnC and TrnD homologues in the context of neighbouring genes encoding potential bacteriocin structural peptides. Moreover, metagenomic analysis revealed that TrnC or TrnD homologs are present in a variety of metagenomic environments, suggesting a widespread distribution of thuricin-like operons in a variety of environments. In-silico analysis of radical SAM proteins is sufficient to identify novel putative sactibiotic clusters

TEAM-UP for quality: a cluster randomized controlled trial protocol focused on preventing pressure ulcers through repositioning frequency and precipitating factors

Background: Pressure ulcers/injuries (PrUs), a critical concern for nursing homes (NH), are responsible for chronic wounds, amputations, septic infections, and premature deaths. PrUs occur most commonly in older adults and NH residence is a risk factor for their development, with at least one of every nine U.S. NH residents experiencing a PrU and many NHs having high incidence and prevalence rates, in some instances well over 20%. PrU direct treatment costs are greater than prevention costs, making prevention-focused protocols critical. Current PrU prevention protocols recommend repositioning residents at moderate, high, and severe risk every 2 h. The advent of visco- elastic (VE) high-density foam support-surfaces over the past decade may now make it possible to extend the repositioning interval to every 3 or 4 h without increasing PrU development. The TEAM-UP (Turn Everyone And Move for Ulcer Prevention) study aims to determine: 1) whether repositioning interval can be extended for NH residents without compromising PrU incidence and 2) how changes in medical severity interact with changes in risk level and repositioning schedule to predict PrU development. Methods: In this proposed cluster randomized study, 9 NHs will be randomly assigned to one of three repositioning intervals (2, 3, or 4 h) for a 4-week period. Each enrolled site will use a single NH-wide repositioning interval as the standard of care for residents at low, moderate, and high risk of PrU development (N = 951) meeting the following criteria: minimum 3-day stay, without PrUs, no adhesive allergy, and using VE support surfaces (mattresses). An FDA-cleared patient monitoring system that records position/movement of these residents via individual wireless sensors will be used to visually cue staff when residents need repositioning and document compliance with repositioning protocols. Discussion: This study will advance knowledge about repositioning frequency and clinically assessed PrU risk level in relation to PrU incidence and medical severity. Outcomes of this research will contribute to future guidelines for more precise preventive nursing practices and refinement of PrU prevention guidelines. Trial registration: Clinical Trial Registration: NCT02996331