A non-pharmacological intervention to manage behavioral and psychological symptoms of dementia and reduce caregiver distress: Design and methods of project ACT3

Project ACT is a randomized controlled trial designed to test the effectiveness of a non-pharmacological home-based intervention to reduce behavioral and psychological symptoms of dementia (BPSD) and caregiver distress. The study targets 272 stressed racially diverse family caregivers providing in-home care to persons with moderate stage dementia with one or more behavioral disturbances. All participants are interviewed at baseline, 4-months (main trial endpoint), and 6-months (maintenance). The four-month intervention involves up to 13 visits from an occupational therapist who works with families to problem-solve potential triggers (communication style, environmental clutter) contributing to behaviors, and instruct in strategies to reduce caregiver stress and manage targeted behaviors. To rule out infection or other potential medical contributors to behaviors, a nurse obtains blood and urine samples from the dementia patient, and conducts a medication review. Participants in the no-treatment control group are offered the nurse arm and one in-home session following trial completion at 6-months. This paper describes the research methods, theoretical and clinical aspects of this multi-component, targeted psycho-social treatment approach, and the measures used to evaluate quality of life improvements for persons with dementia and their families

Differences in the emotional and practical experiences of exclusively breastfeeding and combination feeding mothers

The majority of research examining the barriers to breastfeeding focuses on the physical challenges faced by mothers rather than the risks of encountering negative emotional and practical feeding experiences. We aimed to quantify the emotional and practical experiences of the overall sample of breastfeeding mothers and identify the differences in the emotional and practical experiences of exclusively breastfeeding mothers and combination feeding mothers, by feeding type and intention. Eight hundred forty‐five mothers with infants up to 26 weeks of age and who had initiated breastfeeding were recruited through relevant social media via advertisements providing a link to an online survey. Predictors of emotional experiences included guilt, stigma, satisfaction with feeding method, and the need to defend themselves due to infant feeding choices. Practical predictors included perceived support from health professionals, main sources of infant feeding information, and respect from their everyday environment, workplace, and when breastfeeding in public. Current feeding type and prenatal feeding intention. In the overall sample, 15% of the mothers reported feeling guilty, 38% stigmatized, and 55% felt the need to defend their feeding choice. Binary logit models revealed that guilt and dissatisfaction were directly associated with feeding type, being higher when supplementing with formula. No associations with feeding intention were identified. This study demonstrates a link between current breastfeeding promotion strategies and the emotional state of breastfeeding mothers who supplement with formula to any extent. To minimize the negative impact on maternal well‐being, it is important that future recommendations recognize the challenges that exclusive breastfeeding brings and provide a more balanced and realistic target for mothers

Process evaluation of a peer-led antenatal breastfeeding class for fathers: perceptions of facilitators and participants

Background: The Parent Infant Feeding Initiative (PIFI) was a factorial, randomised controlled trial that aimed to prolong exclusive breastfeeding by targeting expecting fathers. One of the intervention strategies evaluated was a father-focused breastfeeding class facilitated by a male peer facilitator. The aim of this mixed-methods descriptive study was to 1) evaluate the feedback provided from participants of the class and 2) explore the motivations and experiences of volunteer male peer facilitators trained to deliver the class. Methods: Father-focused breastfeeding antenatal (FFAB) classes were conducted in six Western Australian hospitals between August 2015 and December 2016. Following each peer facilitated FFAB class, expecting father participants completed an evaluation form to assess their satisfaction with the format, facilitation and content, in addition to whether their expectations and confidence to manage breastfeeding problems had changed. Feedback to open-ended questions was analysed using content analysis to identify learnings and suggestions for improvements. At the completion of PIFI, individual telephone interviews were undertaken with 14 peer facilitators to gain insight into their motivations for volunteering and experiences of conducting the classes. Transcripts from interviews were analysed using Braun and Clarke’s six phases for thematic analysis. Results: Participant evaluation forms were completed by 678 of the 697 father participants (98%). Overall satisfaction with class format, facilitation and content was high with 90% or more of fathers either strongly agreeing or agreeing with each positively-phrased evaluation item. Class participants enjoyed interacting with other fathers, appreciated validation of their role, were not always aware of the importance of breastfeeding or potential difficulties, valued the anticipatory guidance around what to expect in the early weeks of parenting and appreciated learning practical breastfeeding support strategies. Peer facilitators indicated they felt well prepared and supported to conduct FFAB classes. Analysis of interview transcripts revealed common experiences of the peer facilitators incorporating four themes: ‘Highlights of being a facilitator’, ‘Challenges’, ‘Mourning the project completion’ and ‘Satisfaction with training and support’. Conclusion: Father-focused breastfeeding classes supported by volunteer male peer facilitators are a feasible and acceptable way of engaging fathers as breastfeeding supporters. Trial registration: ACTRN12614000605695. Registered 6 June 2014

Taqman Real-Time PCR Detects Avipoxvirus DNA in Blood of Hawaìi `Amakihi (Hemignathus virens)

Margaret E. M. Farias et al...Background Avipoxvirus sp. is a significant threat to endemic bird populations on several groups of islands worldwide, including Hawaìi, the Galapagos Islands, and the Canary Islands. Accurate identification and genotyping of Avipoxvirus is critical to the study of this disease and how it interacts with other pathogens, but currently available methods rely on invasive sampling of pox-like lesions and may be especially harmful in smaller birds. Methodology/Principal Findings Here, we present a nested TaqMan Real-Time PCR for the detection of the Avipoxvirus 4b core protein gene in archived blood samples from Hawaiian birds. The method was successful in amplifying Avipoxvirus DNA from packed blood cells of one of seven Hawaiian honeycreepers with confirmed Avipoxvirus infections and 13 of 28 Hawaìi `amakihi (Hemignathus virens) with suspected Avipoxvirus infections based on the presence of pox-like lesions. Mixed genotype infections have not previously been documented in Hawaìi but were observed in two individuals in this study. Conclusions/Significance We anticipate that this method will be applicable to other closely related strains of Avipoxvirus and will become an important and useful tool in global studies of the epidemiology of Avipoxvirus.Funding for this study was provided by: U.S. Geological Survey, Pacific Island Ecosystems Research Center (biology.usgs.gov/pierc/); U.S. Geological Survey Wildlife (biology.usgs.gov/wter/) and Invasive Species (biology.usgs.gov/invasive/) Programs; National Science Foundation (DEB0083944, www.nsf.gov); NIH/NCRR IDeA Networks of Biomedical Research Excellence (INBRE), P20RR016467 (http://www.ncrr.nih.gov/research_infrast​ructure/institutional_development_award/​idea_networks_of_biomedical_research_exc​ellence/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Plasma Proteomics of Renal Function: A Transethnic Meta-Analysis and Mendelian Randomization Study.

BACKGROUND: Studies on the relationship between renal function and the human plasma proteome have identified several potential biomarkers. However, investigations have been conducted largely in European populations, and causality of the associations between plasma proteins and kidney function has never been addressed. METHODS: A cross-sectional study of 993 plasma proteins among 2882 participants in four studies of European and admixed ancestries (KORA, INTERVAL, HUNT, QMDiab) identified transethnic associations between eGFR/CKD and proteomic biomarkers. For the replicated associations, two-sample bidirectional Mendelian randomization (MR) was used to investigate potential causal relationships. Publicly available datasets and transcriptomic data from independent studies were used to examine the association between gene expression in kidney tissue and eGFR. RESULTS: In total, 57 plasma proteins were associated with eGFR, including one novel protein. Of these, 23 were additionally associated with CKD. The strongest inferred causal effect was the positive effect of eGFR on testican-2, in line with the known biological role of this protein and the expression of its protein-coding gene (SPOCK2) in renal tissue. We also observed suggestive evidence of an effect of melanoma inhibitory activity (MIA), carbonic anhydrase III, and cystatin-M on eGFR. CONCLUSIONS: In a discovery-replication setting, we identified 57 proteins transethnically associated with eGFR. The revealed causal relationships are an important stepping stone in establishing testican-2 as a clinically relevant physiological marker of kidney disease progression, and point to additional proteins warranting further investigation.The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. This work was also supported by the Biomedical Research Program at Weill Cornell Medicine in Qatar, a program funded by the Qatar Foundation. K.S. is supported by Qatar National Research Fund (QNRF) grant no. NPRPC11-0115-180010. The Nord-Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology NTNU), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health. The HUNT part of the project re-used protein data that was originally analysed and paid for by Somalogic Inc, CO, USA. Somalogic had no role in the design and conduct of the study; collection of phenotypic data, statistical analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Professor John Danesh is funded by the National Institute for Health Research [Senior Investigator Award]. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. RNA-sequencing experiments and kidney gene expression studies were supported by British Heart Foundation project grants [PG/17/35/33001 and PG/19/16/34270] and Kidney Research UK grants [ RP_017_20180302 and RP_013_20190305] to M.T. The German Diabetes Center is funded by the German Federal Ministry of Health (Berlin, Germany), the Ministry of Culture and Science of the state North Rhine-Westphalia (Düsseldorf, Germany), and grants from the German Federal Ministry of Education and Research (Berlin, Germany) to the German Center for Diabetes Research e.V. (DZD)

International Guidelines for Veterinary Tumor Pathology: A Call to Action

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website (www.vetcancerprotocols.org), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care

Sample size considerations for trials using cerebral white matter hyperintensity progression as an intermediate outcome at 1 year after mild stroke: Results of a prospective cohort study

Background: White matter hyperintensities (WMHs) are commonly seen on in brain imaging and are associated with stroke and cognitive decline. Therefore, they may provide a relevant intermediate outcome in clinical trials. WMH can be measured as a volume or visually on the Fazekas scale. We investigated predictors of WMH progression and design of efficient studies using WMH volume and Fazekas score as an intermediate outcome. Methods: We prospectively recruited 264 patients with mild ischaemic stroke and measured WMH volume, Fazekas score, age and cardiovascular risk factors at baseline and 1 year. We modelled predictors of WMH burden at 1 year and used the results in sample size calculations for hypothetical randomised controlled trials with different analysis plans and lengths of follow-up. Results: Follow-up WMH volume was predicted by baseline WMH: a 0.73-ml (95% CI 0.65-0.80, p < 0.0001) increase per 1-ml baseline volume increment, and a 2.93-ml increase (95% CI 1.76-4.10, p < 0.0001) per point on the Fazekas scale. Using a mean difference of 1 ml in WMH volume between treatment groups, 80% power and 5% alpha, adjusting for all predictors and 2-year follow-up produced the smallest sample size (n = 642). Other study designs produced samples sizes from 2054 to 21,270. Sample size calculations using Fazekas score as an outcome with the same power and alpha, as well as an OR corresponding to a 1-ml difference, were sensitive to assumptions and ranged from 2504 to 18,886. Conclusions: Baseline WMH volume and Fazekas score predicted follow-up WMH volume. Study size was smallest using volumes and longer-term follow-up, but this must be balanced against resources required to measure volumes versus Fazekas scores, bias due to dropout and scanner drift. Samples sizes based on Fazekas scores may be best estimated with simulation studies