Citations

SummaryBackgroundClostridium difficile infection (CDI) recurs in 20–30% of patients.AimTo describe the predictors of recurrence in out‐patients with CDI.MethodsOut‐patient cases of CDI in Olmsted County, MN residents diagnosed between 28 June 2007 and 25 June 2010 were identified. Recurrent CDI was defined as recurrence of diarrhoea with a positive C. difficile PCR test from 15 to 56 days after the initial diagnosis with interim resolution of symptoms. Patients who had two positive tests within 14 days were excluded. Cox proportional hazard models were used to assess the association of clinical variables with time to recurrence of CDI.ResultsThe cohort included 520 out‐patients; 104 had recurrent CDI (cumulative incidence of 17.5% by 30 days). Univariate analysis identified increasing age and antibiotic use to be associated with recurrent CDI. Severe CDI, peripheral leucocyte count and change in serum creatinine >1.5‐fold were not. In a multiple variable model, concomitant antibiotic use was associated with risk of recurrent CDI (HR = 5.4, 95% CI 1.6–17.5, P = 0.005), while age (HR per 10 year increase = 1.1, 95% CI 0.9–1.3, P = 0.22); peripheral leucocyte count >15 × 109/L (HR = 1.0, 95% CI 0.5–2.1, P = 0.92); and change in serum creatinine greater than 1.5‐fold (HR = 0.8, 95% CI 0.4–1.5, P = 0.44) were not.ConclusionsAntibiotic use was independently associated with a dramatic risk of recurrent Clostridium difficile infection in an out‐patient cohort. It is important to avoid unnecessary systemic antibiotics in patients with Clostridium difficile infection, and patients with ongoing antibiotic use should be monitored closely for recurrent infection.

ABSTRACT The genome of nonsegmented negative-strand RNA viruses is tightly embedded within a nucleocapsid made of a nucleoprotein (N) homopolymer. To ensure processive RNA synthesis, the viral polymerase L in complex with its cofactor phosphoprotein (P) binds the nucleocapsid that constitutes the functional template. Measles virus P and N interact through two binding sites. While binding of the P amino terminus with the core of N (N CORE ) prevents illegitimate encapsidation of cellular RNA, the interaction between their C-terminal domains, P XD and N TAIL is required for viral RNA synthesis. To investigate the binding dynamics between the two latter domains, the P XD F497 residue that makes multiple hydrophobic intramolecular interactions was mutated. Using a quantitative mammalian protein complementation assay and recombinant viruses, we found that an increase in P XD -to-N TAIL binding strength is associated with a slower transcript accumulation rate and that abolishing the interaction renders the polymerase nonfunctional. The use of a newly developed system allowing conditional expression of wild-type or mutated P genes, revealed that the loss of the P XD -N TAIL interaction results in reduced transcription by preformed transcriptases, suggesting reduced engagement on the genomic template. These intracellular data indicate that the viral polymerase entry into and progression along its genomic template relies on a protein-protein interaction that serves as a tightly controlled dynamic anchor. IMPORTANCE Mononegavirales have a unique machinery to replicate RNA. Processivity of their polymerase is only achieved when the genome template is entirely embedded into a helical homopolymer of nucleoproteins that constitutes the nucleocapsid. The polymerase binds to the nucleocapsid template through the phosphoprotein. How the polymerase complex enters and travels along the nucleocapsid template to ensure uninterrupted synthesis of up to ∼6,700-nucleotide messenger RNAs from six to ten consecutive genes is unknown. Using a quantitative protein complementation assay and a biGene-biSilencing system allowing conditional expression of two P genes copies, the role of the P-to-N interaction in polymerase function was further characterized. We report here a dynamic protein anchoring mechanism that differs from all other known polymerases that rely only onto a sustained and direct binding to their nucleic acid template.

Context Studies that investigate research questions that have already been resolved represent a waste of resources. However, the failure to collect sufficient evidence to resolve a given question results in ambiguity. Objectives The present study was conducted to reanalyse the results of a meta‐analysis of simulation‐based education ( SBE ) to determine: (i) whether researchers continue to replicate research studies after the answer to a research question has become known, and (ii) whether researchers perform enough replications to definitively answer important questions. Methods A systematic search of multiple databases to May 2011 was conducted to identify original research evaluating SBE for health professionals in comparison with no intervention or any active intervention, using skill outcomes. Data were extracted by reviewers working in duplicate. Data synthesis involved a cumulative meta‐analysis to illuminate patterns of evidence by sequentially adding studies according to a variable of interest (e.g. publication year) and re‐calculating the pooled effect size with each addition. Cumulative meta‐analysis by publication year was applied to 592 comparative studies using several thresholds of ‘sufficiency’, including: statistical significance; stable effect size classification and magnitude (Hedges’ g ± 0.1), and precise estimates (confidence intervals of less than ± 0.2). Results Among studies that compared the outcomes of SBE with those of no intervention, evidence supporting a favourable effect of SBE on skills existed as early as 1973 (one publication) and further evidence confirmed a quantitatively large effect of SBE by 1997 (28 studies). Since then, a further 404 studies were published. Among studies comparing SBE with non‐simulation instruction, the effect initially favoured non‐simulation training, but the addition of a third study in 1997 brought the pooled effect to slightly favour simulation, and by 2004 (14 studies) this effect was statistically significant (p < 0.05) and the magnitude had stabilised (small effect). A further 37 studies were published after 2004. By contrast, evidence from studies evaluating repetition continued to show borderline statistical significance and wide confidence intervals in 2011. Conclusions Some replication is necessary to obtain stable estimates of effect and to explore different contexts, but the number of studies of SBE often exceeds the minimum number of replications required.

BACKGROUNDDespite targeted antiemetics, data support an unmet need related to the management of delayed nausea and vomiting (NV). Promising pilot data informed this phase III trial evaluating gabapentin for delayed NV from highly emetogenic chemotherapy (HEC).METHODSParticipants were randomized to receive prophylactic treatment with 20 mg of dexamethasone and a 5HT3 receptor antagonist (RA) on the day of chemotherapy, followed by gabapentin 300 mg twice a day and dexamethasone (dex) or placebo and dex after HEC. Gabapentin/placebo was started the day of chemotherapy and continued through day 5 for the first chemotherapy cycle, whereas dex was titrated down on days 2‐4. The primary end point was complete response (CR), defined as no emesis and no use of rescue medications on days 2‐6, using an NV diary. The percentages of those in each group with a CR were compared by Fisher's exact test.RESULTSFour hundred thirty patients were enrolled in this study. Forty‐seven percent of patients in the gabapentin arm and 41% in the placebo arm had a CR (P = .23). Mean number of emesis episodes was <0.5 daily, and mean nausea severity was < 2 (mild). In both arms, patient satisfaction with NV control was greater than 8 (with 10 being perfectly satisfied). There were no significant differences in unwanted side effects.CONCLUSIONSIn this study, gabapentin did not significantly improve delayed NV. Patients were satisfied with the control of their nausea and vomiting irrespective of arm. The use of a 5HT3 RA and dexamethasone provided good control of nausea and vomiting for most patients. Cancer 2014;120:3575–3583. © 2014 American Cancer Society.

Radial artery access for performance of coronary and peripheral diagnostic as well as interventional procedures is on the rise. With increasing adoption comes the expected increase in procedural complications. We describe a novel, simple, and effective nonpharmacologic solution for sheath entrapment related to pharmaco‐resistant radial artery spasm. © 2014 Wiley Periodicals, Inc.

Background and Purpose— We investigated whether family history of stroke or coronary heart disease (CHD) is associated with presence of carotid artery stenosis (CAS). Methods— The study cohort included 864 patients (72±8 years; 68% men) with CAS and 1698 controls (61±11 years; 55% men) referred for noninvasive vascular testing. CAS was defined as ≥70% stenosis in the internal carotid artery on ultrasound or history of carotid revascularization. Controls did not have CAS or history of cerebrovascular disease or CHD. Family history of stroke and CHD was defined as having ≥1 first-degree relative who had stroke or CHD before age 65 years. Logistic regression analysis was used to evaluate whether family history of stroke or CHD was associated with presence of CAS, independent of conventional risk factors. Results— Family history of stroke and CHD was present more often in patients with CAS than in controls, with a resulting odds ratios (95% confidence interval) of 2.02 (1.61–2.53) and 2.01 (1.70–2.37), respectively. The associations remained significant after adjustment for age, sex, body mass index, smoking, diabetes mellitus, hypertension, and dyslipidemia; odds ratios: 1.41 (1.06–1.90) and 1.69 (1.35–2.10), respectively. A greater number of affected relatives with stroke or CHD was associated with higher odds of CAS; adjusted odds ratios: 1.25 (0.91–1.72) and 1.46 (1.14–1.89) versus 2.65 (1.35–5.40) and 2.13 (1.57–2.90) for patients with 1 and ≥2 affected relatives with stroke and CHD, respectively. Conclusions— Family history of stroke and of CHD were each associated with CAS, suggesting that shared genetic and environmental factors contribute to the risk of CAS.

Abstract Recent evidence indicates that sensory and motor changes may precede the cognitive symptoms of Alzheimer's disease (AD) by several years and may signify increased risk of developing AD. Traditionally, sensory and motor dysfunctions in aging and AD have been studied separately. To ascertain the evidence supporting the relationship between age‐related changes in sensory and motor systems and the development of AD and to facilitate communication between several disciplines, the National Institute on Aging held an exploratory workshop titled “Sensory and Motor Dysfunctions in Aging and AD.” The scientific sessions of the workshop focused on age‐related and neuropathologic changes in the olfactory, visual, auditory, and motor systems, followed by extensive discussion and hypothesis generation related to the possible links among sensory, cognitive, and motor domains in aging and AD. Based on the data presented and discussed at this workshop, it is clear that sensory and motor regions of the central nervous system are affected by AD pathology and that interventions targeting amelioration of sensory‐motor deficits in AD may enhance patient function as AD progresses.

Microscopic colitis (MC) is an umbrella term that encompasses lymphocytic colitis (LC) and collagenous colitis (CC). Several histological variants of these 2 entities exist; among them is the uncommon giant cell colitis (GCC), in which histiocytic giant cells (GCs) are present in background of CC or LC. We report the case of a 71-year-old woman complaining of watery diarrhea for several years that was diagnosed with CC. At follow-up, she developed giant cell colitis (GCC). Nine years later, a colectomy revealed a form of microscopic colitis in which significant intraepithelial lymphocytosis and collagen plate thickening have disappeared while GCs persisted with diffuse mononuclear cells inflammation of the lamina propria. Thinning of the collagen plate in association with GCs has been described previously. The case contributes the possibility of further evolution of MC into a pure giant cell colitis in which the prototypical manifestations of MC have all but disappeared.