Altered Patterns of Fungal Keratitis at a London Ophthalmic Referral Hospital: An Eight-Year Retrospective Observational Study

PURPOSE: In previous studies of fungal keratitis (FK) from temperate countries, yeasts were the predominant isolates, with ocular surface disease (OSD) being the leading risk factor. Since the 2005–2006 outbreak of contact lens (CL)-associated Fusarium keratitis, there may have been a rise in CL-associated filamentary FK in the United Kingdom. This retrospective case series investigated the patterns of FK from 2007 to 2014. We compared these to 1994–2006 data from the same hospital. DESIGN: Retrospective observational study. METHODS: All cases of FK presenting to Moorfields Eye Hospital between 2007 and 2014 were identified. The definition of FK was either a fungal organism isolated by culture or fungal structures identified by light microscopy (LM) of scrape material, histopathology, or in vivo corneal confocal microscopy (IVCM). Main outcome measure was cases of FK per year. RESULTS: A total of 112 patients had confirmed FK. Median age was 47.2 years. Between 2007 and 2014, there was an increase in annual numbers of FK (Poisson regression, P [ .0001). FK was confirmed using various modalities: 79 (70.5%) by positive culture, 16 (14.3%) by LM, and 61 (54.5%) by IVCM. Seventy-eight patients (69.6%) were diagnosed with filamentary fungus alone, 28 (25%) with yeast alone, and 6 (5.4%) with mixed filamentary and yeast infections. This represents an increase in the proportion of filamentary fungal infections from the pre-2007 data. Filamentary fungal and yeast infections were associated with CL use and OSD, respectively. CONCLUSIONS: The number of FK cases has increased. This increase is due to CL-associated filamentary FK. Clinicians should be aware of these changes, which warrant epidemiologic investigations to identify modifiable risk factors

Altered Patterns of Fungal Keratitis at a London Ophthalmic Referral Hospital: An Eight-Year Retrospective Observational Study.

PURPOSE: In previous studies of fungal keratitis (FK) from temperate countries, yeasts were the predominant isolates, with ocular surface disease (OSD) being the leading risk factor. Since the 2005-2006 outbreak of contact lens (CL)-associated Fusarium keratitis, there may have been a rise in CL-associated filamentary FK in the United Kingdom. This retrospective case series investigated the patterns of FK from 2007 to 2014. We compared these to 1994-2006 data from the same hospital. DESIGN: Retrospective observational study. METHODS: All cases of FK presenting to Moorfields Eye Hospital between 2007 and 2014 were identified. The definition of FK was either a fungal organism isolated by culture or fungal structures identified by light microscopy (LM) of scrape material, histopathology, or in vivo corneal confocal microscopy (IVCM). Main outcome measure was cases of FK per year. RESULTS: A total of 112 patients had confirmed FK. Median age was 47.2 years. Between 2007 and 2014, there was an increase in annual numbers of FK (Poisson regression, P = .0001). FK was confirmed using various modalities: 79 (70.5%) by positive culture, 16 (14.3%) by LM, and 61 (54.5%) by IVCM. Seventy-eight patients (69.6%) were diagnosed with filamentary fungus alone, 28 (25%) with yeast alone, and 6 (5.4%) with mixed filamentary and yeast infections. This represents an increase in the proportion of filamentary fungal infections from the pre-2007 data. Filamentary fungal and yeast infections were associated with CL use and OSD, respectively. CONCLUSIONS: The number of FK cases has increased. This increase is due to CL-associated filamentary FK. Clinicians should be aware of these changes, which warrant epidemiologic investigations to identify modifiable risk factors

CD74-dependent Deregulation of the Tumor Suppressor Scribble in Human Epithelial and Breast Cancer Cells

The γ subunit of the major histocompatibility complex (MHC) class II complex, CD74, is overexpressed in a significant proportion of metastatic breast tumors, but the mechanistic foundation and biologic significance of this phenomenon are not fully understood. Here, we show that when CD74 is overexpressed in human cancer and noncancerous epithelial cells, it interacts and interferes with the function of Scribble, a product of a well-known tumor suppressor gene. Furthermore, using epithelial cell lines expressing CD74 under the control of tetracycline-inducible promoter and quantitative high-resolution mass spectrometry, we demonstrate that, as a result of CD74 overexpression, the phosphorylation pattern of the C-terminal part of Scribble undergoes specific changes. This is accompanied with a translocation of the protein from the sites of cell-to-cell contacts at the plasma membrane to the cytoplasm, which is likely to effectively enhance the motility and invasiveness of the cancer cells. © 2013 Neoplasia Press, Inc. All rights reserved

The influence of 'significant others' on persistent back pain and work participation: a qualitative exploration of illness perceptions

Background Individual illness perceptions have been highlighted as important influences on clinical outcomes for back pain. However, the illness perceptions of 'significant others' (spouse/partner/close family member) are rarely explored, particularly in relation to persistent back pain and work participation. The aim of this study was to initiate qualitative research in this area in order to further understand these wider influences on outcome. Methods Semi-structured interviews based on the chronic pain version of the Illness Perceptions Questionnaire-Revised were conducted with a convenience sample of UK disability benefit claimants, along with their significant others (n=5 dyads). Data were analysed using template analysis. Results Significant others shared, and perhaps further reinforced, claimants' unhelpful illness beliefs including fear of pain/re-injury associated with certain types of work and activity, and pessimism about the likelihood of return to work. In some cases, significant others appeared more resigned to the permanence and negative inevitable consequences of the claimant's back pain condition on work participation, and were more sceptical about the availability of suitable work and sympathy from employers. In their pursuit of authenticity, claimants were keen to stress their desire to work whilst emphasising how the severity and physical limitations of their condition prevented them from doing so. In this vein, and seemingly based on their perceptions of what makes a 'good' significant other, significant others acted as a 'witness to pain', supporting claimants' self-limiting behaviour and statements of incapacity, often responding with empathy and assistance. The beliefs and responses of significant others may also have been influenced by their own experience of chronic illness, thus participants lives were often intertwined and defined by illness. Conclusions The findings from this exploratory study reveal how others and wider social circumstances might contribute both to the propensity of persistent back pain and to its consequences. This is an area that has received little attention to date, and wider support of these findings may usefully inform the design of future intervention programmes aimed at restoring work participation

Placental Structure in Type 1 Diabetes: Relation to Fetal Insulin, Leptin, and IGF-I

OBJECTIVE-Alteration of placental structure may influence fetal overgrowth and complications of maternal diabetes. We examined the placenta in a cohort of offspring of mothers with type I diabetes (OT1DM) to assess structural changes and determine whether these were related to maternal A1C, fetal hematocrit, fetal hormonal, or metabolic axes. RESEARCH DESIGN AND METHODS-Placental samples were analyzed using stereological techniques to quantify volumes and surface areas of key placental components in 88 OT1DM and 39 control subjects, and results related to maternal A1C and umbilical cord analytes (insulin, leptin, adiponectin, IGF-I, hematocrit, lipids, C-reactive protein, and interleukin-6). RESULTS-Intervillous space volume was increased in OT1DM (OT1DM 250 +/- 81 cm(3) VS. control 217 +/- 65 cm(3); P = 0.02) with anisomorphic growth of villi (P = 0.025). The placentas showed a trend to increased weight (OT1DM 690 +/- 19 g; control 641 +/- 22 g; P = 0.08), but villous, nonparenchymal, trophoblast, and capillary volumes did not differ. Villous surface area, capillary surface area, membrane thickness, and calculated morphometric diffusing capacity were also similar in type 1 diabetic and control subjects. A1C at 26-34 weeks associated with birth weight (r = 0.27, P = 0.03), placental weight (r = 0.41, P = 0.0009), and intervillous space volume (r = 0.38, P = 0.0024). In multivariate analysis of cord parameters in OT1DM, fetal IGF-I emerged as a significant correlate of most components (intervillous space, villous, trophoblast, and capillary volumes, all P < 0.01). By contrast, fetal insulin was only independently associated with capillary surface area (positive, r(2) = 6.7%; P = 0.02). CONCLUSIONS-There are minimal placental structural differences between OT1DM and control subjects. Fetal IGF-I but not fetal insulin emerges as a key correlate of placental substructural volumes, thereby facilitating feedback to the placenta regarding fetal metabolic deman

Synthesis and Monte Carlo Structure Determination of SSZ-77: A New Zeolite Topology

A new molecular sieve topology has been determined from a multistage Monte Carlo computer simulation procedure using the program ZEFSAII. The material, SSZ-77, consists of alternating layers present in the RUT and AST topologies, and intergrowths may be possible in the way that this material grows. The product first arose from a synthesis where it appears that the degradation of the quaternary ammonium structure directing agent (SDA) produced the viable organo-guest molecule in the structure formation. The synthesis requires the use of Ge as well as Si as lattice components. In the absence of Ge, only RUT forms. An additional study was carried out to determine the suitable size of guest molecules in a series spanning trimethylamine to tetraethylammonium in the presence of benzyltrimethylammonium. It is found from NMR investigations that none of the larger molecules are occluded within the cages of the SSZ-77 structure, and that the primary occluded species is trimethylamine or tetramethylammonium

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72,694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, Large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), %body fat and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate-to-vigorous physical activity (MVPA), vigorous activity and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia and ponderal index, without heterogeneity (all: I-square=0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95%CI: 0.94, 0.98) respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. This article is protected by copyright. All rights reserved.Includes MRC, Wellcome Trust and NIHR

Cost-effectiveness of non-invasive methods for assessment and monitoring of liver fibrosis and cirrhosis in patients with chronic liver disease: systematic review and economic evaluation

BACKGROUND: Liver biopsy is the reference standard for diagnosing the extent of fibrosis in chronic liver disease; however, it is invasive, with the potential for serious complications. Alternatives to biopsy include non-invasive liver tests (NILTs); however, the cost-effectiveness of these needs to be established. OBJECTIVE: To assess the diagnostic accuracy and cost-effectiveness of NILTs in patients with chronic liver disease. DATA SOURCES: We searched various databases from 1998 to April 2012, recent conference proceedings and reference lists. METHODS: We included studies that assessed the diagnostic accuracy of NILTs using liver biopsy as the reference standard. Diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was conducted using the bivariate random-effects model with correlation between sensitivity and specificity (whenever possible). Decision models were used to evaluate the cost-effectiveness of the NILTs. Expected costs were estimated using a NHS perspective and health outcomes were measured as quality-adjusted life-years (QALYs). Markov models were developed to estimate long-term costs and QALYs following testing, and antiviral treatment where indicated, for chronic hepatitis B (HBV) and chronic hepatitis C (HCV). NILTs were compared with each other, sequential testing strategies, biopsy and strategies including no testing. For alcoholic liver disease (ALD), we assessed the cost-effectiveness of NILTs in the context of potentially increasing abstinence from alcohol. Owing to a lack of data and treatments specifically for fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), the analysis was limited to an incremental cost per correct diagnosis. An analysis of NILTs to identify patients with cirrhosis for increased monitoring was also conducted. RESULTS: Given a cost-effectiveness threshold of £20,000 per QALY, treating everyone with HCV without prior testing was cost-effective with an incremental cost-effectiveness ratio (ICER) of £9204. This was robust in most sensitivity analyses but sensitive to the extent of treatment benefit for patients with mild fibrosis. For HBV [hepatitis B e antigen (HBeAg)-negative)] this strategy had an ICER of £28,137, which was cost-effective only if the upper bound of the standard UK cost-effectiveness threshold range (£30,000) is acceptable. For HBeAg-positive disease, two NILTs applied sequentially (hyaluronic acid and magnetic resonance elastography) were cost-effective at a £20,000 threshold (ICER: £19,612); however, the results were highly uncertain, with several test strategies having similar expected outcomes and costs. For patients with ALD, liver biopsy was the cost-effective strategy, with an ICER of £822. LIMITATIONS: A substantial number of tests had only one study from which diagnostic accuracy was derived; therefore, there is a high risk of bias. Most NILTs did not have validated cut-offs for diagnosis of specific fibrosis stages. The findings of the ALD model were dependent on assuptions about abstinence rates assumptions and the modelling approach for NAFLD was hindered by the lack of evidence on clinically effective treatments. CONCLUSIONS: Treating everyone without NILTs is cost-effective for patients with HCV, but only for HBeAg-negative if the higher cost-effectiveness threshold is appropriate. For HBeAg-positive, two NILTs applied sequentially were cost-effective but highly uncertain. Further evidence for treatment effectiveness is required for ALD and NAFLD. STUDY REGISTRATION: This study is registered as PROSPERO CRD42011001561. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Clinical Problems in the Hospitalized Parkinson's Disease Patient: Systematic Review

The problems Parkinson's disease (PD) patients encounter when admitted to a hospital, are known to be numerous and serious. These problems have been inventoried through a systematic review of literature on reasons for emergency and hospital admissions in PD patients, problems encountered during hospitalization, and possible solutions for the encountered problems using the Pubmed database. PD patients are hospitalized in frequencies ranging from 7 to 28% per year. PD/parkinsonism patients are approximately one and a half times more frequently and generally 2 to 14 days longer hospitalized than non-PD patients. Acute events occurring during hospitalization were mainly urinary infection, confusion, and pressure ulcers. Medication errors were also frequent adverse events. During and after surgery PD patients had an increased incidence of infections, confusion, falls, and decubitus, and 31% of patients was dissatisfied in the way their PD was managed. There are only two studies on medication continuation during surgery and one analyzing the effect of an early postoperative neurologic consultation, and numerous case reports, and opinionated views and reviews including other substitutes for dopaminergic medication intraoperatively. In conclusion, most studies were retrospective on small numbers of patients. The major clinical problems are injuries, infections, poor control of PD, and complications of PD treatment. There are many (un-researched) proposals for improvement. A substantial number of PD patients' admissions might be prevented. There should be guidelines concerning the hospitalized PD patients, with accent on early neurological consultation and team work between different specialities, and incorporating nonoral dopaminergic replacement therapy when necessary. © 2011 Movement Disorder Societ