Systematic review of antiepileptic drugs’ safety and effectiveness in feline epilepsy

Understanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs’ efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total

What happens for informal caregivers during transition to increased levels of care for the person with dementia? A systematic review protocol

Abstract Background Dementia is a globally prevalent disease that requires ongoing and increasing levels of care, often provided in the first instance by informal caregivers. Supporting transitions in informal caregiving in dementia is a pertinent issue for caregivers, care providers and governments. There is no existing systematic review that seeks to identify and map the body of literature regarding the review question: ‘What happens for informal caregivers during transition to increased levels of care for the person with dementia?’ Methods/design ASSIA, CINAHL+, MEDLINE, PsycINFO, SCIE, Social Service Abstracts and Web of Science will be systematically searched. Specialist dementia research libraries will be contacted. Reviews identified as relevant during the search process, their reference lists, and reference lists of accepted papers will be hand-searched. Qualitative, quantitative and mixed methods studies that seek to represent the experiences of, or examine the impact upon, informal caregivers during transition to increased formal care for the person with dementia will be eligible for inclusion. Synthesis will be segregated into qualitative and quantitative papers. Findings will be summarised, and the review will be prepared for publication. Discussion The review will seek to identify potentially vulnerable groups in need of support and as such, inform the practice of those offering support. It will also inform future research by highlighting areas in which current literature is insubstantial. Systematic review registration PROSPERO CRD4201706724

Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk

Introduction: Lung cancer is the world’s leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. / Methods and analysis: Using a single-consent Zelen’s design, ever-smokers aged 55–80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. / Ethics and dissemination: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. / Trial registration numbers: ISRCTN42704678 and NCT03750110

Splash!: a prospective birth cohort study of the impact of environmental, social and family-level influences on child oral health and obesity related risk factors and outcomes

Background: Dental caries (decay) is the most prevalent disease of childhood. It is often left untreated and can impact negatively on general health, and physical, developmental, social and learning outcomes. Similar to other health issues, the greatest burden of dental caries is seen in those of low socio-economic position. In addition, a number of diet-related risk factors for dental caries are shared risk factors for the development of childhood obesity. These include high and frequent consumption of refined carbohydrates (predominately sugars), and soft drinks and other sweetened beverages, and low intake of (fluoridated) water. The prevalence of childhood obesity is also at a concerning level in most countries and there is an opportunity to determine interventions for addressing both of these largely preventable conditions through sustainable and equitable solutions. This study aims to prospectively examine the impact of drink choices on child obesity risk and oral health status.Methods/Design: This is a two-stage study using a mixed methods research approach. The first stage involves qualitative interviews of a sub-sample of recruited parents to develop an understanding of the processes involved in drink choice, and inform the development of the Discrete Choice Experiment analysis and the measurement instruments to be used in the second stage. The second stage involves the establishment of a prospective birth cohort of 500 children from disadvantaged communities in rural and regional Victoria, Australia (with and without water fluoridation). This longitudinal design allows measurement of changes in the child&rsquo;s diet over time, exposure to fluoride sources including water, dental caries progression, and the risk of childhood obesity.Discussion: This research will provide a unique contribution to integrated health, education and social policy and program directions, by providing clearer policy relevant evidence on strategies to counter social and environmental factors which predispose infants and children to poor health, wellbeing and social outcomes; and evidence-based strategies to promote health and prevent disease through the adoption of healthier lifestyles and diet. Further, given the absence of evidence on the processes and effectiveness of contemporary policy implementation, such as community water fluoridation in rural and regional communities it&rsquo;s approach and findings will be extremelyinformative.<br /

Efficacy and Safety of Prophylactic Vaccines against Cervical HPV Infection and Diseases among Women: A Systematic Review & Meta-Analysis

<p>Abstract</p> <p>Background</p> <p>We conducted a systematic review and meta-analysis to assess efficacy and safety of prophylactic HPV vaccines against cervical cancer precursor events in women.</p> <p>Methods</p> <p>Randomized-controlled trials of HPV vaccines were identified from MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts and references of identified studies, and assessed by two independent reviewers. Efficacy data were synthesized using fixed-effect models, and evaluated for heterogeneity using I²statistic.</p> <p>Results</p> <p>Seven unique trials enrolling 44,142 females were included. The fixed-effect Relative Risk (RR) and 95% confidence intervals were 0.04 (0.01-0.11) and 0.10 (0.03-0.38) for HPV-16 and HPV 18-related CIN2+ in the per-protocol populations (PPP). The corresponding RR was 0.47 (0.36-0.61) and 0.16 (0.08-0.34) in the intention-to-treat populations (ITT). Efficacy against CIN1+ was similar in scale in favor of vaccine. Overall vaccines were highly efficacious against 6-month persistent infection with HPV 16 and 18, both in the PPP cohort (RR: 0.06 [0.04-0.09] and 0.05 [0.03-0.09], respectively), and the ITT cohorts (RR: 0.15 [0.10-0.23] and 0.24 [0.14-0.42], respectively). There was limited prophylactic effect against CIN2+ and 6-month persistent infections associated with non-vaccine oncogenic HPV types. The risk of serious adverse events (RR: 1.00, 0.91-1.09) or vaccine-related serious adverse events (RR: 1.82; 0.79-4.20) did not differ significantly between vaccine and control groups. Data on abnormal pregnancy outcomes were underreported.</p> <p>Conclusions</p> <p>Prophylactic HPV vaccines are safe, well tolerated, and highly efficacious in preventing persistent infections and cervical diseases associated with vaccine-HPV types among young females. However, long-term efficacy and safety needs to be addressed in future trials.</p

The MicroRNA-200 Family Is Upregulated in Endometrial Carcinoma

BACKGROUND: MicroRNAs (miRNAs, miRs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. MicroRNAs are dysregulated in cancer and may play essential roles in tumorigenesis. Additionally, miRNAs have been shown to have prognostic and diagnostic value in certain types of cancer. The objective of this study was to identify dysregulated miRNAs in endometrioid endometrial adenocarcinoma (EEC) and the precursor lesion, complex atypical hyperplasia (CAH). METHODOLOGY: We compared the expression profiles of 723 human miRNAs from 14 cases of EEC, 10 cases of CAH, and 10 normal proliferative endometria controls using Agilent Human miRNA arrays following RNA extraction from formalin-fixed paraffin-embedded (FFPE) tissues. The expression of 4 dysregulated miRNAs was validated using real time reverse transcription-PCR. RESULTS: Forty-three miRNAs were dysregulated in EEC and CAH compared to normal controls (p<0.05). The entire miR-200 family (miR-200a/b/c, miR-141, and miR-429) was up-regulated in cases of EEC. CONCLUSIONS: This information contributes to the candidate miRNA expression profile that has been generated for EEC and shows that certain miRNAs are dysregulated in the precursor lesion, CAH. These miRNAs in particular may play important roles in tumorigenesis. Examination of miRNAs that are consistently dysregulated in various studies of EEC, like the miR-200 family, will aid in the understanding of the role that miRNAs play in tumorigenesis in this tumour type

MiR-200c Regulates Noxa Expression and Sensitivity to Proteasomal Inhibitors

The pro-apoptotic p53 target Noxa is a BH3-only protein that antagonizes the function of selected anti-apoptotic Bcl-2 family members. While much is known regarding the transcriptional regulation of Noxa, its posttranscriptional regulation remains relatively unstudied. In this study, we therefore investigated whether Noxa is regulated by microRNAs. Using a screen combining luciferase reporters, bioinformatic target prediction analysis and microRNA expression profiling, we identified miR-200c as a negative regulator of Noxa expression. MiR-200c was shown to repress basal expression of Noxa, as well as Noxa expression induced by various stimuli, including proteasomal inhibition. Luciferase reporter experiments furthermore defined one miR-200c target site in the Noxa 3′UTR that is essential for this direct regulation. In spite of the miR-200c:Noxa interaction, miR-200c overexpression led to increased sensitivity to the clinically used proteasomal inhibitor bortezomib in several cell lines. This apparently contradictory finding was reconciled by the fact that in cells devoid of Noxa expression, miR-200c overexpression had an even more pronounced positive effect on apoptosis induced by proteasomal inhibition. Together, our data define miR-200c as a potentiator of bortezomib-induced cell death. At the same time, we show that miR-200c is a novel negative regulator of the pro-apoptotic Bcl-2 family member Noxa

Risk factors for breast cancer in postmenopausal Caucasian and Chinese-Canadian women

Abstract Introduction Striking differences exist between countries in the incidence of breast cancer. The causes of these differences are unknown, but because incidence rates change in migrants, they are thought to be due to lifestyle rather than genetic differences. The goal of this cross-sectional study was to examine breast cancer risk factors in populations with different risks for breast cancer. Methods We compared breast cancer risk factors among three groups of postmenopausal Canadian women at substantially different risk of developing breast cancer - Caucasians (N = 413), Chinese women born in the West or who migrated to the West before age 21 (N = 216), and recent Chinese migrants (N = 421). Information on risk factors and dietary acculturation were collected by telephone interviews using questionnaires, and anthropometric measurements were taken at a home visit. Results Compared to Caucasians, recent Chinese migrants weighed on average 14 kg less, were 6 cm shorter, had menarche a year later, were more often parous, less often had a family history of breast cancer or a benign breast biopsy, a higher Chinese dietary score, and a lower Western dietary score. For most of these variables, Western born Chinese and early Chinese migrants had values intermediate between those of Caucasians and recent Chinese migrants. We estimated five-year absolute risks for breast cancer using the Gail Model and found that risk estimates in Caucasians would be reduced by only 11% if they had the risk factor profile of recent Chinese migrants for the risk factors in the Gail Model. Conclusions Our results suggest that in addition to the risk factors in the Gail Model, there likely are other factors that also contribute to the large difference in breast cancer risk between Canada and China