Burden of Illness in UK Subjects with Reported Respiratory Infections Vaccinated or Unvaccinated against Influenza: A Retrospective Observational Study

<div><p>Objective</p><p>Detailed data are lacking on influenza burden in the United Kingdom (UK). The objective of this study was to estimate the disease burden associated with influenza-like illness (ILI) in the United Kingdom stratified by age, risk and influenza vaccination status.</p><p>Methods</p><p>This retrospective, cross-sectional, exploratory, observational study used linked data from the General Practice Research Database and the Hospital Episode Statistics databases to estimate resource use and cost associated with ILI in the UK.</p><p>Results</p><p>Data were included from 156,193 patients with ≥1 general practitioner visit with ILI. There were 21,518 high-risk patients, of whom 12,514 (58.2%) were vaccinated and 9,004 (41.8%) were not vaccinated, and 134,675 low-risk patients, of whom 17,482 (13.0%) were vaccinated and 117,193 (87.0%) were not vaccinated. High-risk vaccinated patients were older (p<0.001) and had more risk conditions (p<0.001). High-risk (odds ratio [OR] 2.16) or vaccinated (OR 1.19) patients had a higher probability of >1 general practitioner visit compared with low-risk and unvaccinated patients. Patients who were high-risk and vaccinated had a reduced risk of >1 general practitioner visit (OR 0.82; p<0.001). High-risk individuals who were also vaccinated had a lower probability of ILI-related hospitalisation than individuals who were high-risk or vaccinated alone (OR 0.59). In people aged ≥65 years, the mortality rate was lower in vaccinated than unvaccinated individuals (OR 0.75). The cost of ILI-related GP visits and hospital admissions in the UK over the study period in low-risk vaccinated patients was £27,391,142 and £141,932,471, respectively. In low-risk unvaccinated patients the corresponding values were £168,318,709 and £112,534,130, respectively.</p><p>Conclusions</p><p>Although vaccination rates in target groups have increased, many people are still not receiving influenza vaccination, and the burden of ILI in the United Kingdom remains substantial. Improving influenza vaccination uptake may have the potential to reduce this burden.</p></div

Adverse events in people taking macrolide antibiotics versus placebo for any indication

BACKGROUND: Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated. Because adverse events are treatment-specific, rather than disease-specific, it is possible to increase the number of adverse events available for analysis by combining randomised controlled trials (RCTs) of the same treatment across different diseases. OBJECTIVES:To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Acute Respiratory Infections Group Specialised Register (2018, Issue 4); MEDLINE (Ovid, from 1946 to 8 May 2018); Embase (from 2010 to 8 May 2018); CINAHL (from 1981 to 8 May 2018); LILACS (from 1982 to 8 May 2018); and Web of Science (from 1955 to 8 May 2018). We searched clinical trial registries for current and completed trials (9 May 2018) and checked the reference lists of included studies and of previous Cochrane Reviews on macrolides. SELECTION CRITERIA: We included RCTs that compared a macrolide antibiotic to placebo for any indication. We included trials using any of the four most commonly used macrolide antibiotics: azithromycin, clarithromycin, erythromycin, or roxithromycin. Macrolides could be administered by any route. Concomitant medications were permitted provided they were equally available to both treatment and comparison groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and collected data. We assessed the risk of bias of all included studies and the quality of evidence for each outcome of interest. We analysed specific adverse events, deaths, and subsequent carriage of macrolide-resistant bacteria separately. The study participant was the unit of analysis for each adverse event. Any specific adverse events that occurred in 5% or more of any group were reported. We undertook a meta-analysis when three or more included studies reported a specific adverse event. MAIN RESULTS: We included 183 studies with a total of 252,886 participants (range 40 to 190,238). The indications for macrolide antibiotics varied greatly, with most studies using macrolides for the treatment or prevention of either acute respiratory tract infections, cardiovascular diseases, chronic respiratory diseases, gastrointestinal conditions, or urogynaecological problems. Most trials were conducted in secondary care settings. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin.Most studies (89%) reported some adverse events or at least stated that no adverse events were observed.Gastrointestinal adverse events were the most commonly reported type of adverse event. Compared to placebo, macrolides caused more diarrhoea (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.34 to 2.16; low-quality evidence); more abdominal pain (OR 1.66, 95% CI 1.22 to 2.26; low-quality evidence); and more nausea (OR 1.61, 95% CI 1.37 to 1.90; moderate-quality evidence). Vomiting (OR 1.27, 95% CI 1.04 to 1.56; moderate-quality evidence) and gastrointestinal disorders not otherwise specified (NOS) (OR 2.16, 95% CI 1.56 to 3.00; moderate-quality evidence) were also reported more often in participants taking macrolides compared to placebo.The number of additional people (absolute difference in risk) who experienced adverse events from macrolides was: gastrointestinal disorders NOS 85/1000; diarrhoea 72/1000; abdominal pain 62/1000; nausea 47/1000; and vomiting 23/1000.The number needed to treat for an additional harmful outcome (NNTH) ranged from 12 (95% CI 8 to 23) for gastrointestinal disorders NOS to 17 (9 to 47) for abdominal pain; 19 (12 to 33) for diarrhoea; 19 (13 to 30) for nausea; and 45 (22 to 295) for vomiting.There was no clear consistent difference in gastrointestinal adverse events between different types of macrolides or route of administration.Taste disturbances were reported more often by participants taking macrolide antibiotics, although there were wide confidence intervals and moderate heterogeneity (OR 4.95, 95% CI 1.64 to 14.93; Iand#178; = 46%; low-quality evidence).Compared with participants taking placebo, those taking macrolides experienced hearing loss more often, however only four studies reported this outcome (OR 1.30, 95% CI 1.00 to 1.70; Iand#178; = 0%; low-quality evidence).We did not find any evidence that macrolides caused more cardiac disorders (OR 0.87, 95% CI 0.54 to 1.40; very low-quality evidence); hepatobiliary disorders (OR 1.04, 95% CI 0.27 to 4.09; very low-quality evidence); or changes in liver enzymes (OR 1.56, 95% CI 0.73 to 3.37; very low-quality evidence) compared to placebo.We did not find any evidence that appetite loss, dizziness, headache, respiratory symptoms, blood infections, skin and soft tissue infections, itching, or rashes were reported more often by participants treated with macrolides compared to placebo.Macrolides caused less cough (OR 0.57, 95% CI 0.40 to 0.80; moderate-quality evidence) and fewer respiratory tract infections (OR 0.70, 95% CI 0.62 to 0.80; moderate-quality evidence) compared to placebo, probably because these are not adverse events, but rather characteristics of the indications for the antibiotics. Less fever (OR 0.73, 95% 0.54 to 1.00; moderate-quality evidence) was also reported by participants taking macrolides compared to placebo, although these findings were non-significant.There was no increase in mortality in participants taking macrolides compared with placebo (OR 0.96, 95% 0.87 to 1.06; Iand#178; = 11%; low-quality evidence).Only 24 studies (13%) provided useful data on macrolide-resistant bacteria. Macrolide-resistant bacteria were more commonly identified among participants immediately after exposure to the antibiotic. However, differences in resistance thereafter were inconsistent.Pharmaceutical companies supplied the trial medication or funding, or both, for 91 trials. AUTHORS' CONCLUSIONS: The macrolides as a group clearly increased rates of gastrointestinal adverse events. Most trials made at least some statement about adverse events, such as "none were observed". However, few trials clearly listed adverse events as outcomes, reported on the methods used for eliciting adverse events, or even detailed the numbers of people who experienced adverse events in both the intervention and placebo group. This was especially true for the adverse event of bacterial resistance.</p

Meta-analysis of northeast Atlantic marine taxa shows contrasting phylogeographic patterns following post-LGM expansions

Background. Comparative phylogeography enables the study of historical and evolutionary processes that have contributed to shaping patterns of contemporary genetic diversity across co-distributed species. In this study, we explored genetic structure and historical demography in a range of coastal marine species across the northeast Atlantic to assess whether there are commonalities in phylogeographic patterns across taxa and to evaluate whether the timings of population expansions were linked to the Last Glacial Maximum (LGM). Methods. A literature search was conducted using Web of Science. Search terms were chosen to maximise the inclusion of articles reporting on population structure and phylogeography from the northeast Atlantic; titles and abstracts were screened to identify suitable articles within the scope of this study. Given the proven utility of mtDNA in comparative phylogeography and the availability of these data in the public domain, a meta-analysis was conducted using published mtDNA gene sequences. A standardised methodology was implemented to ensure that the genealogy and demographic history of all mtDNA datasets were reanalysed in a consistent and directly comparable manner. Results. Mitochondrial DNA datasets were built for 21 species. The meta-analysis revealed significant population differentiation in 16 species and four main types of haplotype network were found, with haplotypes in some species unique to specific geographical locations. A signal of rapid expansion was detected in 16 species, whereas five species showed evidence of a stable population size. Corrected mutation rates indicated that the majority of expansions were estimated to have occurred after the earliest estimate for the LGM (similar to 26.5 Kyr), while few expansions were estimated to have pre-dated the LGM. Conclusion. This study suggests that post-LGM expansion appeared to be common in a range of marine taxa, supporting the concept of rapid expansions after the LGM as the ice sheets started to retreat. However, despite the commonality of expansion patterns in many of these taxa, phylogeographic patterns appear to differ in the species included in this study. This suggests that species-specific evolutionary processes, as well as historical events, have likely influenced the distribution of genetic diversity of marine taxa in the northeast Atlantic

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Development and Functional Analysis of Novel Genetic Promoters Using DNA Shuffling, Hybridization and a Combination Thereof

BACKGROUND: Development of novel synthetic promoters with enhanced regulatory activity is of great value for a diverse range of plant biotechnology applications. METHODOLOGY: Using the Figwort mosaic virus full-length transcript promoter (F) and the sub-genomic transcript promoter (FS) sequences, we generated two single shuffled promoter libraries (LssF and LssFS), two multiple shuffled promoter libraries (LmsFS-F and LmsF-FS), two hybrid promoters (FuasFScp and FSuasFcp) and two hybrid-shuffled promoter libraries (LhsFuasFScp and LhsFSuasFcp). Transient expression activities of approximately 50 shuffled promoter clones from each of these libraries were assayed in tobacco (Nicotiana tabacum cv. Xanthi) protoplasts. It was observed that most of the shuffled promoters showed reduced activity compared to the two parent promoters (F and FS) and the CaMV35S promoter. In silico studies (computer simulated analyses) revealed that the reduced promoter activities of the shuffled promoters could be due to their higher helical stability. On the contrary, the hybrid promoters FuasFScp and FSuasFcp showed enhanced activities compared to F, FS and CaMV 35S in both transient and transgenic Nicotiana tabacum and Arabidopsis plants. Northern-blot and qRT-PCR data revealed a positive correlation between transcription and enzymatic activity in transgenic tobacco plants expressing hybrid promoters. Histochemical/X-gluc staining of whole transgenic seedlings/tissue-sections and fluorescence images of ImaGene Green™ treated roots and stems expressing the GUS reporter gene under the control of the FuasFScp and FSuasFcp promoters also support the above findings. Furthermore, protein extracts made from protoplasts expressing the human defensin (HNP-1) gene driven by hybrid promoters showed enhanced antibacterial activity compared to the CaMV35S promoter. SIGNIFICANCE/CONCLUSION: Both shuffled and hybrid promoters developed in the present study can be used as molecular tools to study the regulation of ectopic gene expression in plants

Social factors influencing Russian male alcohol use over the life course: a qualitative study investigating age based social norms, masculinity, and workplace context

The massive fluctuations occurring in Russian alcohol-related mortality since the mid-1980s cannot be seen outside of the context of great social and economic change. There is a dearth of qualitative studies about Russian male drinking and especially needed are those that address social processes and individual changes in drinking. Conducted as part of a longitudinal study on men’s alcohol consumption in Izhevsk, this qualitative study uses 25 semi-structured biographical interviews with men aged 33–60 years to explore life course variation in drinking. The dominant pattern was decreasing binge and frequent drinking as men reached middle age which was precipitated by family building, reductions in drinking with work colleagues, and health concerns. A minority of men described chaotic drinking histories with periods of abstinence and heavy drinking. The results highlight the importance of the blue-collar work environment for conditioning male heavy drinking in young adulthood through a variety of social, normative and structural mechanisms. Post-Soviet changes had a structural influence on the propensity for workplace drinking but the important social function of male drinking sessions remained. Bonding with workmates through heavy drinking was seen as an unavoidable and essential part of young men’s social life. With age peer pressure to drink decreased and the need to perform the role of responsible breadwinner put different behavioural demands on men. For some resisting social pressure to drink became an important site of self-determination and a mark of masculine maturity. Over the lifetime the place where masculine identity was asserted shifted from the workplace to the home, which commonly resulted in a reduction in drinking. We contribute to existing theories of Russian male drinking by showing that the performance of age-related social roles influences Russian men’s drinking patterns, drinking contexts and their attitudes. Further research should be conducted investigating drinking trajectories in Russian men

Estimation and uncertainty analyses of grassland biomass in Northern China: Comparison of multiple remote sensing data sources and modeling approaches

Accurate estimation of grassland biomass and its dynamics are crucial not only for the biogeochemical dynamics of terrestrial ecosystems, but also for the sustainable use of grassland resources. However, estimations of grassland biomass on large spatial scale usually suffer from large variability and mostly lack quantitative uncertainty analyses. In this study, the spatial grassland biomass estimation and its uncertainty were assessed based on 265 field measurements and remote sensing data across Northern China during 2001-2005. Potential sources of uncertainty, including remote sensing data sources (DATsrc), model forms (MODfrm) and model parameters (biomass allocation, BMallo, e.g. root:shoot ratio), were determined and their relative contribution was quantified. The results showed that the annual grassland biomass in Northern China was 1268.37 +/- 180.84Tg (i.e., 532.02 +/- 99.71 g/m(2)) during 2001-2005, increasing from western to eastern area, with a mean relative uncertainty of 19.8%. There were distinguishable differences among the uncertainty contributions of three sources (BMallo >DATsrc>MODfrm), which contributed 52%, 27% and 13%, respectively. This study highlighted the need to concern the uncertainty in grassland biomass estimation, especially for the uncertainty related to BMallo. (C) 2015 Elsevier Ltd. All rights reserved

Determinants of preventable readmissions in the United States: a systematic review

<p>Abstract</p> <p>Background</p> <p>Hospital readmissions are a leading topic of healthcare policy and practice reform because they are common, costly, and potentially avoidable events. Hospitals face the prospect of reduced or eliminated reimbursement for an increasing number of preventable readmissions under nationwide cost savings and quality improvement efforts. To meet the current changes and future expectations, organizations are looking for potential strategies to reduce readmissions. We undertook a systematic review of the literature to determine what factors are associated with preventable readmissions.</p> <p>Methods</p> <p>We conducted a review of the English language medicine, health, and health services research literature (2000 to 2009) for research studies dealing with unplanned, avoidable, preventable, or early readmissions. Each of these modifying terms was included in keyword searches of readmissions or rehospitalizations in Medline, ISI, CINAHL, The Cochrane Library, ProQuest Health Management, and PAIS International. Results were limited to US adult populations.</p> <p>Results</p> <p>The review included 37 studies with significant variation in index conditions, readmitting conditions, timeframe, and terminology. Studies of cardiovascular-related readmissions were most common, followed by all cause readmissions, other surgical procedures, and other specific-conditions. Patient-level indicators of general ill health or complexity were the commonly identified risk factors. While more than one study demonstrated preventable readmissions vary by hospital, identification of many specific organizational level characteristics was lacking.</p> <p>Conclusions</p> <p>The current literature on preventable readmissions in the US contains evidence from a variety of patient populations, geographical locations, healthcare settings, study designs, clinical and theoretical perspectives, and conditions. However, definitional variations, clear gaps, and methodological challenges limit translation of this literature into guidance for the operation and management of healthcare organizations. We recommend that those organizations that propose to reward reductions in preventable readmissions invest in additional research across multiple hospitals in order to fill this serious gap in knowledge of great potential value to payers, providers, and patients.</p

Conduct disorder in girls: neighborhoods, family characteristics, and parenting behaviors

<p>Abstract</p> <p>Background</p> <p>Little is known about the social context of girls with conduct disorder (CD), a question of increasing importance to clinicians and researchers. The purpose of this study was to examine the associations between three social context domains (neighborhood, family characteristics, and parenting behaviors) and CD in adolescent girls, additionally testing for race moderation effects. We predicted that disadvantaged neighborhoods, family characteristics such as parental marital status, and parenting behaviors such as negative discipline would characterize girls with CD. We also hypothesized that parenting behaviors would mediate the associations between neighborhood and family characteristics and CD.</p> <p>Methods</p> <p>We recruited 93 15–17 year-old girls from the community and used a structured psychiatric interview to assign participants to a CD group (n = 52) or a demographically matched group with no psychiatric disorder (n = 41). Each girl and parent also filled out questionnaires about neighborhood, family characteristics, and parenting behaviors.</p> <p>Results</p> <p>Neighborhood quality was not associated with CD in girls. Some family characteristics (parental antisociality) and parenting behaviors (levels of family activities and negative discipline) were characteristic of girls with CD, but notll. There was no moderation by race. Our hypothesis that the association between family characteristics and CD would be mediated by parenting behaviors was not supported.</p> <p>Conclusion</p> <p>This study expanded upon previous research by investigating multiple social context domains in girls with CD and by selecting a comparison group who were not different in age, social class, or race. When these factors are thus controlled, CD in adolescent girls is not significantly associated with neighborhood, but is associated with some family characteristics and some types of parental behaviors. However, the mechanisms underlying these relationships need to be further investigated. We discuss possible explanations for our findings and suggest directions for future research.</p

Dietary reference values for sodium

Following a request from the European Commission, the EFSA Panel&nbsp;on Nutrition, Novel Foods and Food Allergens (NDA) derived dietary reference values (DRVs) for sodium. Evidence from balance studies on sodium and on the relationship between sodium intake and health outcomes, in particular cardiovascular disease (CVD)-related endpoints and bone health, was reviewed. The data were not sufficient to enable an average requirement (AR) or population reference intake (PRI) to be derived. However, by integrating the available evidence and associated uncertainties, the Panel&nbsp;considers that a sodium intake of 2.0&nbsp;g/day represents a level of sodium for which there is sufficient confidence in a reduced risk of CVD in the general adult population. In addition, a sodium intake of 2.0&nbsp;g/day is likely to allow most of the general adult population to maintain sodium balance. Therefore, the Panel&nbsp;considers that 2.0&nbsp;g sodium/day is a safe and adequate intake for the general EU population of adults. The same value applies to pregnant and lactating women. Sodium intakes that are considered safe and adequate for children are extrapolated from the value for adults, adjusting for their respective energy requirement and including a growth factor, and are as follows: 1.1&nbsp;g/day for children aged 1\u20133&nbsp;years, 1.3&nbsp;g/day for children aged 4\u20136&nbsp;years, 1.7&nbsp;g/day for children aged 7\u201310&nbsp;years and 2.0&nbsp;g/day for children aged 11\u201317&nbsp;years, respectively. For infants aged 7\u201311&nbsp;months, an Adequate Intake (AI) of 0.2&nbsp;g/day is proposed based on upwards extrapolation of the estimated sodium intake in exclusively breast-fed infants aged 0\u20136&nbsp;months