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Although individually uncommon, rare diseases (RDs) collectively affect 6-8% of the population. The unmet need of the rare disease community was recognized by the European Commission which in 2012 funded three flagship projects, RD-Connect, NeurOmics, and EURenOmics, to help move the field forward with the ambition of advancing -omics research and data sharing at their core in line with the goals of IRDiRC (International Rare Disease Research Consortium). NeurOmics and EURenOmics generate -omics data and improve diagnosis and therapy in rare renal and neurological diseases, with RD-Connect developing an infrastructure to facilitate the sharing, systematic integration and analysis of these data. Here, we summarize the achievements of these three projects, their impact on the RD community and their vision for the future. We also report from the Joint Outreach Day organized by the three projects on the 3rd of May 2017 in Berlin. The workshop stimulated an open, multi-stakeholder discussion on the challenges of the rare diseases, and highlighted the cross-project cooperation and the common goal: the use of innovative genomic technologies in rare disease research.

Background: Human, animal, and cell experimental studies; human biomarker studies; and genetic studies complement epidemiologic findings and can offer insights into biological plausibility and pathways between exposure and disease, but methods for synthesizing such studies are lacking. We, therefore, developed a methodology for identifying mechanisms and carrying out systematic reviews of mechanistic studies that underpin exposure–cancer associations. Methods: A multidisciplinary team with expertise in informatics, statistics, epidemiology, systematic reviews, cancer biology, and nutrition was assembled. Five 1-day workshops were held to brainstorm ideas; in the intervening periods we carried out searches and applied our methods to a case study to test our ideas. Results: We have developed a two-stage framework, the first stage of which is designed to identify mechanisms underpinning a specific exposure–disease relationship; the second stage is a targeted systematic review of studies on a specific mechanism. As part of the methodology, we also developed an online tool for text mining for mechanism prioritization (TeMMPo) and a new graph for displaying related but heterogeneous data from epidemiologic studies (the Albatross plot). Conclusions: We have developed novel tools for identifying mechanisms and carrying out systematic reviews of mechanistic studies of exposure–disease relationships. In doing so, we have outlined how we have overcome the challenges that we faced and provided researchers with practical guides for conducting mechanistic systematic reviews. Impact: The aforementioned methodology and tools will allow potential mechanisms to be identified and the strength of the evidence underlying a particular mechanism to be assessed. Cancer Epidemiol Biomarkers Prev; 26(11); 1667–75. ©2017 AACR.

IntroductionDespite the observed and theoretical advantages of shared decision-making in a range of clinical contexts, including contraceptive care, there remains a paucity of evidence on how to facilitate its adoption. This paper describes the protocol for a study to assess the comparative effectiveness of patient-targeted and provider-targeted interventions for facilitating shared decision-making about contraceptive methods.Methods and analysisWe will conduct a 2×2 factorial cluster randomised controlled trial with four arms: (1) video+prompt card, (2) decision aids+training, (3) video+prompt cardanddecision aids+training and (4) usual care. The clusters will be clinics in USA that deliver contraceptive care. The participants will be people who have completed a healthcare visit at a participating clinic, were assigned female sex at birth, are aged 15–49 years, are able to read and write English or Spanish and have not previously participated in the study. The primary outcome will be shared decision-making about contraceptive methods. Secondary outcomes will be the occurrence of a conversation about contraception in the healthcare visit, satisfaction with the conversation about contraception, intended contraceptive method(s), intention to use a highly effective method, values concordance of the intended method(s), decision regret, contraceptive method(s) used, use of a highly effective method, use of the intended method(s), adherence, satisfaction with the method(s) used, unintended pregnancy and unwelcome pregnancy. We will collect study data via longitudinal patient surveys administered immediately after the healthcare visit, four weeks later and six months later.Ethics and disseminationWe will disseminate results via presentations at scientific and professional conferences, papers published in peer-reviewed, open-access journals and scientific and lay reports. We will also make an anonymised copy of the final participant-level dataset available to others for research purposes.Trial registration numberClinicalTrials.gov Identifier:NCT02759939.

Introduction: P2X3 antagonism with MK-7264 (formerly AF 219) has demonstrated cough frequency reduction in chronic cough patients. We evaluated MK-7264 on cough reflex sensitivity to evoked tussive challenge. Methods: In this Phase 2, double-blind, 2-period study, chronic cough subjects (CC) and healthy volunteers (HV) underwent baseline challenge with ATP, citric acid, capsaiscin, and water fog (randomized order) before randomization to single-dose MK-7264 100 mg or placebo (PBO) in crossover fashion (≥ 1 week washout between study days). Concentration of challenge agents inducing ≥2 (C2) and ≥5 (C5) coughs were recorded. Cough frequency and Cough Severity Visual Analogue Scale (VAS; 100 mm) were secondary endpoints. Adverse events (AE) were monitored. Results: 24 CC (mean age 61 years) and 12 HV (mean age 38 years) were randomized. Cough challenge threshold significantly increased for ATP by 4.7 fold (C2; p=0.0006) and 3.7 fold (C5; p=0.0067) for MK-7264 vs. PBO in CC; C2 and C5 only increased 2 fold in HV. Water fog C2 and C5 increased significantly (p Conclusions: Purine ATP-evoked cough was significantly inhibited by MK-7264 100 mg; Cough count and severity reduction support its rapid onset and high potency in subjects with clinically important chronic cough. Results for evoked cough by other agents challenge their usefulness in antitussive drug discovery.

Background The availability and effectiveness of decision aids (DAs) on early abortion methods remain unknown, despite their potential for supporting women's decision making. Objective To describe the availability, impact and quality of DAs on surgical and medical early abortion methods for women seeking induced abortion. Search strategy For the systematic review, we searched MEDLINE, Cochrane Library, CINAHL, EMBASE and PsycINFO. For the environmental scan, we searched Google and App Stores and consulted key informants. Inclusion criteria For the systematic review, we included studies evaluating an early abortion method DA (any format and language) vs a comparison group on women's decision making. DAs must have met the Stacey et al (2014). Cochrane review definition of DAs. For the environmental scan, we included English DAs developed for the US context. Data extraction and synthesis We extracted study and DA characteristics, assessed study quality using the Effective Practice and Organization of Care risk of bias tool and assessed DA quality using International Patient Decision Aid Standards (IPDAS). Results The systematic review identified one study, which found that the DA group had higher knowledge and felt more informed. The evaluated DA met few IPDAS criteria. In contrast, the environmental scan identified 49 DAs created by non-specialists. On average, these met 28% of IPDAS criteria for Content, 22% for Development and 0% for Effectiveness. Conclusions Research evaluating DAs on early abortion methods is lacking, and although many tools are accessible, they demonstrate suboptimal quality. Efforts to revise existing or develop new DAs, support patients to identify high-quality DAs and facilitate non-specialist developers' adoption of best practices for DA development are needed.

Advance care planning (ACP) is a structured discussion about a person's wishes and thoughts for the future, and is recognised as a vital part of good care at the end of life ( Department of Health 2008 , Royal College of Physicians et al 2009 , General Medical Council 2010 ).

Despite recent rapid advances in sequencing technologies, a significant proportion of patients with rare genetic disorders do not receive a genetic diagnosis after exhaustive testing, and even fewer have a potential therapeutic target identified. Taking rare neuromuscular and neurodegenerative disorders as a paradigm that can be extended to other rare Mendelian disorders, this viewpoint explores the opportunities that are brought about by the integration of genomics and proteomics, as well as the limitations and remaining challenges of this newly emerging field of proteogenomics. The relevance of combining proteomic findings with genetic results for diagnosis and gene discovery is illustrated, highlighting the insights the combined analysis provides into the underlying biology and aetiology as well as the limitations of the experimental techniques. A final discussion focuses on the importance of mechanisms to enable the sharing, reuse, and analysis of source experimental data and describes some of the international initiatives that are making progress in this area.

This study explores the effectiveness of an education programme, Let Me Decide, designed to support the development of advance care planning (ACP) for people with cognitive impairment and frailty.

This study explores experiences of and views of healthcare decision-making in the past, present and future among people with dementia and their family carers.

Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy worldwide with complex, multi-systemic, and progressively worsening symptoms. There is currently no treatment for this inherited disorder and research can be challenging due to the rarity and variability of the disease. The UK Myotonic Dystrophy Patient Registry is a patient self-enrolling online database collecting clinical and genetic information. For this cross-sectional “snapshot” analysis, 556 patients with a confirmed diagnosis of DM1 registered between May 2012 and July 2016 were included. An almost even distribution was seen between genders and a broad range of ages was present from 8 months to 78 years, with the largest proportion between 30 and 59 years. The two most frequent symptoms were fatigue and myotonia, reported by 79 and 78% of patients, respectively. The severity of myotonia correlated with the severity of fatigue as well as mobility impairment, and dysphagia occurred mostly in patients also reporting myotonia. Men reported significantly more frequent severe myotonia, whereas severe fatigue was more frequently reported by women. Cardiac abnormalities were diagnosed in 48% of patients and more than one-third of them needed a cardiac implant. Fifteen percent of patients used a non-invasive ventilation and cataracts were removed in 26% of patients, 65% of which before the age of 50 years. The registry’s primary aim was to facilitate and accelerate clinical research. However, these data also allow us to formulate questions for hypothesis-driven research that may lead to improvements in care and treatment. Electronic supplementary material The online version of this article (doi:10.1007/s00415-017-8483-2) contains supplementary material, which is available to authorized users.

Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care. In the rare diseases field, the vast majority of diseases are caused by destructive but previously difficult to identify protein-coding gene mutations. The reduction in cost of genetic testing and advances in the clinical use of genome sequencing, data science and imaging are converging to provide more precise understandings of the ‘person-time-place’ triad. That is: who is affected (people); when the disease is occurring (time); and where the disease is occurring (place). Consequently we are witnessing a paradigm shift in public health policy and practice towards ‘precision public health’.

Contains fulltext : 170010.pdf (Publisher’s version ) (Open Access) BACKGROUND: Shared decision-making (SDM) has become a policy priority, yet its implementation is not routinely assessed. To address this gap we tested the delivery of CollaboRATE, a 3-item patient reported experience measure of SDM, via multiple survey modes. OBJECTIVE: To assess CollaboRATE response rates and respondent characteristics across different modes of administration, impact of mode and patient characteristics on SDM performance and cost of administration per response in a real-world primary care practice. DESIGN: Observational study design, with repeated assessment of SDM performance using CollaboRATE in a primary care clinic over 15 months of data collection. Different modes of administration were introduced sequentially including paper, patient portal, interactive voice response (IVR) call, text message and tablet computer. PARTICIPANTS: Consecutive patients >/=18 years, or parents/guardians of patients

Patient registries are an essential tool to increase current knowledge regarding rare diseases. Understanding these data is a vital step to improve patient treatments and to create the most adequate tools for personalized medicine. However, the growing number of disease-specific patient registries brings also new technical challenges. Usually, these systems are developed as closed data silos, with independent formats and models, lacking comprehensive mechanisms to enable data sharing. To tackle these challenges, we developed a Semantic Web based solution that allows connecting distributed and heterogeneous registries, enabling the federation of knowledge between multiple independent environments. This semantic layer creates a holistic view over a set of anonymised registries, supporting semantic data representation, integrated access, and querying. The implemented system gave us the opportunity to answer challenging questions across disperse rare disease patient registries. The interconnection between those registries using Semantic Web technologies benefits our final solution in a way that we can query single or multiple instances according to our needs. The outcome is a unique semantic layer, connecting miscellaneous registries and delivering a lightweight holistic perspective over the wealth of knowledge stemming from linked rare disease patient registries. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under Grant Agreement no.305444—the RD-Connect project. Pedro Sernadela is funded by Fundac¸ao para a Ci ˜ encia e Tecnologia (FCT) under the ˆGrant Agreement SFRH/BD/52484/2014. Lorena Gonzalez- ´Castro is funded by the Xunta de Galicia, including funding from the operative program FSE Galicia 2007–2013, under the Grant Agreement IN809A 19/2015.

Aims The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers.

Introduction: New omics technologies enabling the efficient, low-cost and large-scale generation and analysis of biomedical data have revolutionised research in rare diseases, offering new methods to identify novel disease and modifier genes, elucidate disease mechanisms, discover biomarkers, and ultimately identify novel therapeutic targets.Areas covered: An overview is provided of the omics fields of relevance for rare disease: genomics, transcriptomics, proteomics, metabolomics and pharmacogenomics. This is followed by a discussion of the challenges that remain in maximising the potential of these technologies and translating them to clinical benefit, particularly the requirement for large-scale collaboration and data sharing.Expert opinion: The rapid uptake of omics approaches has resulted in major advances in rare disease research and led to an exponential growth in data generation. Data analysis and interpretation is now the major rate-limiting step, and the development of integrated approaches in w...

A 25-yr-old, nulliparous, female Przewalski's wild horse (Equus ferus przewalskii) with a history of pituitary pars intermedia dysfunction and recent onset of serosanguinous vaginal discharge was euthanized after a period of lethargy and inappetance. Postmortem examination confirmed an infiltrative uterine adenocarcinoma, which is an uncommon neoplasia in equids. Reproductive disease is significant in this species as they are considered endangered by IUCN. Reproductive soundness and success are paramount to conservation efforts.

We evaluated the effect of gefapixant on cough reflex sensitivity to evoked tussive challenge.In this phase 2, double-blind, two-period study, patients with chronic cough (CC) and healthy volunteers (HV) were randomised to single-dose gefapixant 100 mg or placebo in a crossover fashion. Sequential inhalational challenges with ATP, citric acid, capsaicin and distilled water were performed 1, 3 and 5 h after dosing. Mean concentrations evoking ≥2 coughs (C2) and ≥5 coughs (C5) post dose versus baseline were co-primary endpoints. Objective cough frequency (coughs·h−1) over 24 h and a cough severity visual analogue scale (VAS) were assessed in CC patients. Adverse events were monitored.24 CC patients and 12 HV were randomised (mean age 61 and 38 years, respectively). The cough challenge threshold increased for ATP by 4.7-fold (C2, p≤0.001) and 3.7-fold (C5, p=0.007) for gefapixant versus placebo in CC patients; in HV, C2 and C5 increased 2.4-fold (C2, p=0.113; C5, p=0.003). The distilled water C2 and C5 thresholds increased significantly (pversus placebo in CC patients. Dysgeusia was the most frequent adverse event (75% of HV and 67% of CC patients).ATP-evoked cough was significantly inhibited by gefapixant 100 mg, demonstrating peripheral target engagement. Cough count and severity were reduced in CC patients. Distilled water may also evoke cough through a purinergic pathway.

Uterine adenomyosis was diagnosed in five southern three-banded armadillos (Tolypeutes matacus) from four different zoological collections in North America between 1995 and 2012. Two cases were diagnosed after ovariohysterectomy and histopathologic evaluation of the uteri, and the remaining cases were identified incidentally at the time of postmortem examination. Animals ranged from 5 to 14 yr of age at the time of diagnosis. Of armadillos diagnosed before postmortem examination, clinical signs included weakness, collapse, anemia, and vulvar discharge. Histopathologic evaluation of the uteri revealed well-developed, irregular endometrial glands extending into the myometrium and occasional hemorrhage within these glands. The two cases diagnosed antemortem were successfully treated with ovariohysterectomy. To the authors' knowledge, this condition has not been previously reported in Xenarthra, including armadillos.

Purpose: Signal transducer and activator of transcription 3 (STAT3) plays a critical role in initiation and progression of pancreatic cancer. However, therapeutically targeting STAT3 has failed clinically. We previously identified HAb18G/CD147 as an effective target for cancer treatment. In this study, we aimed to investigate the potential role of HAb18G/CD147 in STAT3-involved pancreatic tumorigenesis in vitro and in vivo. Experimental Design: The expression of HAb18G/CD147, pSTAT3, and CD44s was determined in tissue microarrays. The tumorigenic function and molecular signaling mechanism of HAb18G/CD147 were assessed by in vitro cellular and clonogenic growth, reporter assay, immunoblot assay, immunofluorescence staining, immunoprecipitation, and in vivo tumor formation using loss or gain-of-function strategies. Results: Highly expressed HAb18G/CD147 promoted cellular and clonogenic growth in vitro and tumorigenicity in vivo. Cyclophilin A (CyPA), a ligand of CD147, stimulated STAT3 phosphorylation and its downstream genes cyclin D1/survivin through HAb18G/CD147-dependent mechanisms. HAb18G/CD147 was associated and colocalized with cancer stem cell marker CD44s in lipid rafts. The inhibitors of STAT3 and survivin, as well as CD44s neutralizing antibodies suppressed the HAb18G/CD147-induced cell growth. High HAb18G/CD147 expression in pancreatic cancer was significantly correlated with the poor tumor differentiation, and the high coexpression of HAb18G/CD147-CD44s-STAT3 associated with poor survival of patients with pancreatic cancer. Conclusions: We identified HAb18G/CD147 as a novel upstream activator of STAT3, which interacts with CD44s and plays a critical role in the development of pancreatic cancer. The data suggest that HAb18G/CD147 could be a promising therapeutic target for highly aggressive pancreatic cancer and a surrogate marker in the STAT3-targeted molecular therapies. Clin Cancer Res; 19(24); 6703–15. ©2013 AACR.

Developing quantitative skills, or being academically numerate, is part of the curriculum agenda in science teaching and learning. For many of our students, being asked to ‘do maths’ as part of ‘doing science’ leads to disengagement from learning. Notions of ‘I can't do maths’ speak of a rigidity of mind, a ‘standoff’, forming a barrier to learning in science that needs to be addressed if we, as science educators, are to offer solutions to the so-called ‘maths problem’ and to support students as they move from being novice to expert. Moving from novice to expert is complex and we lean on several theoretical frameworks (thinking dispositions, threshold concepts and mindfulness in learning) to characterize this pathway in science, with a focus on quantitative skills. Fluid thinking and application of numeracy skills are required to manipulate experimental data sets and are integral to our science practice; we need to stop students from seeing them as optional ‘maths’ or ‘statistics’ tasks within our discipl...

Intestinal or cloacal strictures that resulted in intestinal obstruction were diagnosed in six green sea turtles (Chelonia mydas) from three rehabilitation facilities and two zoologic parks. The etiologies of the strictures were unknown in these cases. It is likely that anatomic adaptations of the gastrointestinal tract unique to the green sea turtle's herbivorous diet, paired with causes of reduced intestinal motility, may predispose the species to intestinal damage and subsequent obstructive intestinal disease. In aquarium-maintained green sea turtles, obesity, diet, reduced physical activity, chronic intestinal disease, and inappropriate or inadequate antibiotics might also be potential contributing factors. Clinical, radiographic, and hematologic abnormalities common among most of these sea turtles include the following: positive buoyancy; lethargy; inappetence; regurgitation; obstipation; dilated bowel and accumulation of oral contrast material; anemia; hypoglycemia; hypoalbuminemia; hypocalcemia; and elevated creatine kinase, aspartate aminotransferase, and blood urea nitrogen. Although these abnormalities are nonspecific with many possible contributing factors, intestinal disease, including strictures, should be considered a differential in green sea turtles that demonstrate all or a combination of these clinical findings. Although diagnostic imaging, including radiographs, computed tomography, or magnetic resonance imaging, are important in determining a cause for suspected gastrointestinal disease and identifying an anatomic location of obstruction, intestinal strictures were not successfully identified when using these imaging modalities. Lower gastrointestinal contrast radiography, paired with the use of oral contrast, was useful in identifying the suspected site of intestinal obstruction in two cases. Colonoscopy was instrumental in visually diagnosing intestinal stricture in one case. Therefore, lower gastrointestinal contrast radiography and colonoscopy should be considered in green turtles when gastrointestinal obstructions are suspected. Although partial strictures of the cloacal opening may be identified on gross examination and might be managed with appropriate medical treatment, surgical intervention or humane euthanasia are likely the only options for sea turtles once small or large intestinal strictures have formed.

Objective: To investigate the relationship between women’s postnatal psychological well-being and retrospective, self-reported satisfaction with intrapartum care and the birth experience. Background: The period immediately following childbirth can be marked by various problems that can affect a woman’s happiness and functioning. Previous research has suggested that aspects of the maternal experience of childbirth may act as predictors for specific indicators of women’s postnatal functioning. This study aimed to determine the relationship between satisfaction with labour and birth care and the general childbirth experience and a broad, comprehensive measure of subsequent psychological functioning. Methods: Data for this study was taken from relevant items in the Having a Baby in Queensland 2009 Pilot Survey. Researchers assessed maternal socio-demographic characteristics, perceptions of labour and birth care, satisfaction with labour and birth care, and perceived positivity of the birth experience. A dicho...

Contains fulltext : 159364.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Measuring the process of shared decision making is a challenge, which constitutes a barrier to research and implementation. The aim of the study was to report the development of CollaboRATE, brief patient-reported measure of shared decision making. METHODS: We used the following stages: (1) item formulation; (2) cognitive interviews; (3) item refinement; and (4) pilot testing of final items. Participants were over 18 years old, recruited from the public areas of the Dartmouth-Hitchcock Medical Center. RESULTS: The key finding of this study is that developing a brief patient-reported measure of shared decision making requires a move away from terms such as 'decisions', 'options' and 'preferences'. Although technically correct, these terms act as barriers. They are often unfamiliar, and they also implicitly assume that patients are willing to take active roles in decision making; whereas patients are often unaware that decisions are required, or have taken place, never mind feel that they could or should have participated in them. CONCLUSION: These methods have allowed us to develop a brief, patient-reported measure of shared decision making that is highly accessible to intended users. PRACTICE IMPLICATIONS: The potential strength of the CollaboRATE will be the ability for completion in less than 30s, and across a range of routine settings.

Next-generation sequencing is radically changing how DNA diagnostic laboratories operate. What started as a single-gene profession is now developing into gene panel sequencing and whole exome and genome sequencing (WES/WGS) analyses. With further advances in sequencing technology and concomitant price reductions, whole genome sequencing (WGS) will soon become the standard and be routinely offered. Here we focus on the critical steps involved in performing WGS, with a particular emphasis on points where WGS differs from WES, the important variables that should be taken into account, and the quality control measures that can be taken to monitor the process. The points discussed here, combined with recent publications on guidelines for reporting variants, will facilitate the routine implementation of WGS into a diagnostic setting. This article is protected by copyright. All rights reserved. ispartof: Human Mutation vol:38 issue:8 pages:912-921 ispartof: location:United States status: published

Background: Most studies examining determinants of rising rates of caesarean section have examined patterns in documented reasons for caesarean over time in a single location. Further insights could be gleaned from cross-cultural research that examines practice patterns in locations with disparate rates of caesarean section at a single time point. Methods: We compared both rates of and main reason for pre-labour and intrapartum caesarean between England and Queensland, Australia, using data from retrospective cross-sectional surveys of women who had recently given birth in England (n = 5,250) and Queensland (n = 3,467). Results: Women in Queensland were more likely to have had a caesarean birth (36.2%) than women in England (25.1% of births; OR = 1.44, 95% CI = 1.28-1.61), after adjustment for obstetric characteristics. Between-country differences were found for rates of pre-labour caesarean (21.2% vs. 12.2%) but not for intrapartum caesarean or assisted vaginal birth. Compared to women in England, women in Queensland with a history of caesarean were more likely to have had a pre-labour caesarean and more likely to have had an intrapartum caesarean, due only to a previous caesarean. Among women with no previous caesarean, Queensland women were more likely than women in England to have had a caesarean due to suspected disproportion and failure to progress in labour. Conclusions The higher rates of caesarean birth in Queensland are largely attributable to higher rates of caesarean for women with a previous caesarean, and for the main reason of having had a previous caesarean. Variation between countries may be accounted for by the absence of a single, comprehensive clinical guideline for caesarean section in Queensland.

Duchenne muscular dystrophy (DMD) is a progressive, genetically determined neuromuscular disease that affects males and leads to severe physical disability in early teenage years. Over the last decades, patient-reported outcomes such as Health-Related Quality of Life (HRQoL) gained great interest in clinical research. However, little is known about factors affecting HRQoL in boys with DMD. Data from the multi-center CARE-NMD project of boys with DMD from six European countries collected between 2011 and 2012 were analyzed (8-17 years old; n = 321). HRQoL was measured using the KIDSCREEN-10 index, the Pediatric Quality of Life Inventory (PedsQL) and the Neuromuscular Module of the PedsQL (NMM). Linear regression models served to examine influences of socio-demographic, disease- and treatment-specific as well as participation- and environment-related factors on overall and disease-specific HRQoL. Proportions of explained variance varied across models using different outcomes (18-34%). Overall HRQoL according to the KIDSCREEN-10 index was associated with household income, the frequency of attending a clinic with specialized staff, the number of days spent outside home, and the attitude of the local community, but no significant association with age occurred. Overall HRQoL according to the generic PedsQL and disease-specific HRQoL were both positively associated with age and influenced by the country of residence, the disease stage, number of days spent outside home, and the attitude of the local community. Our results may be relevant for clinical practice and planning interventions for this population, but should be confirmed by future research. Further questions for future studies on boys with DMD are proposed.

BACKGROUND: Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. OBJECTIVE: To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. METHODS: Search methods: For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase, were searched through to June 2010. References of Included studies and reviews were also checked. Selection criteria: Trials fulfilled the following criteria: 1) randomized with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Data collection and analysis: Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. MAIN RESULTS: This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I2 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants). This did not alter with sub-grouping or sensitivity analysis. Few studies compared reduced with modified fat diets, so direct comparison was not possible. AUTHORS' CONCLUSIONS: The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear.

Contains fulltext : 172291.pdf (Publisher’s version ) (Open Access) BACKGROUND/AIM: Given the need for access to patient-facing materials in multiple languages, this study aimed to develop and pilot test an accurate and understandable translation of CollaboRATE, a three-item patient-reported measure of shared decision-making, for Spanish-speaking patients in the United States (US). METHOD: We followed the Translate, Review, Adjudicate, Pre-test, Document (TRAPD) survey translation protocol. Cognitive interviews were conducted with Spanish-speaking adults within an urban Massachusetts internal medicine clinic. For the pilot test, all patients with weekday appointments between May 1 and May 29, 2015 were invited to complete CollaboRATE in either English or Spanish upon exit. We calculated the proportion of respondents giving the best score possible on CollaboRATE and compared scores across key patient subgroups. RESULTS: Four rounds of cognitive interviews with 26 people were completed between January and April 2015. Extensive, iterative refinements to survey items between interview rounds led to final items that were generally understood by participants with diverse educational backgrounds. Pilot data collection achieved an overall response rate of 73 percent, with 606 (49%) patients completing Spanish CollaboRATE questionnaires and 624 (51%) patients completing English CollaboRATE questionnaires. The proportion of respondents giving the best score possible on CollaboRATE was the same (86%) for both the English and Spanish versions of the instrument. DISCUSSION: Our translation method, guided by emerging best practices in survey and health measurement translation, encompassed multiple levels of review. By conducting four rounds of cognitive interviews with iterative item refinement between each round, we arrived at a Spanish language version of CollaboRATE that was understandable to a majority of cognitive interview participants and was completed by more than 600 pilot questionnaire respondents.

Congenital myopathies are a group of inherited muscle disorders characterized by hypotonia, weakness and a non-dystrophic muscle biopsy with the presence of one or more characteristic histological features. Neuromuscular transmission defects have recently been reported in several patients with congenital myopathies (CM). Mutations in KLHL40 are among the most common causes of severe forms of nemaline myopathy. Clinical features of affected individuals include fetal akinesia or hypokinesia, respiratory failure, and swallowing difficulties at birth. Muscle weakness is usually severe and nearly half of the individuals have no spontaneous antigravity movement. The average age of death has been reported to be 5 months in a recent case series. Herein we present a case of a patient with a nemaline myopathy due to KLHL40 mutations (c.604delG, p.Ala202Argfs*56 and c.1513G > C, p.Ala505Pro) with an impressive and prolonged beneficial response to treatment with high-dose pyridostigmine. Myasthenic features or response to ACEI have not previously been reported as a characteristic of nemaline myopathy or KLHL40-related myopathy.

Background women who birth in private facilities in Australia are more likely to have a caesarean birth than women who birth in public facilities and these differences remain after accounting for sector differences in the demographic and health risk profiles of women. However, the extent to which women's preferences and/or freedom to choose their mode of birth further account for differences in the likelihood of caesarean birth between the sectors remains untested. Method women who birthed in Queensland, Australia during a two-week period in 2009 were mailed a self-report survey approximately 3 months after birth. Seven hundred and fifty-seven women provided cross-sectional retrospective data on where they birthed (public or private facility), mode of birth (vaginal or caesarean) and risk factors, along with their preferences and freedom to choose their mode of birth. A hierarchical logistic regression was conducted to determine the extent to which maternal risk and freedom to choose one's mode of birth explain sector differences in the likelihood of having a caesarean birth. Findings while there was no sector difference in women's preference for mode of birth, women who birthed in private facilities had higher odds of feeling able to choose either a vaginal or caesarean birth, and feeling able to choose only a caesarean birth. Women had higher odds of having caesarean birth if they birthed in private facilities, even after accounting for significant risk factors such as age, body mass index, previous caesarean and use of assisted reproductive technology. However, there was no association between place of birth and odds of having a caesarean birth after also accounting for freedom to choose one's mode of birth. Conclusions these findings call into question suggestions that the higher caesarean birth rate in the private sector in Australia is attributable to increased levels of obstetric risk among women birthing in the private sector or maternal preferences alone. Instead, the determinants of sector differences in the likelihood of caesarean births are complex and are linked to differences in the perceived choices for mode of birth between women birthing in the private and public systems.

In a small college town in western Virginia, writer Anthony Restivo searches for unmediated honesty through his very public endurance art. In the midst of media attention, misinformation, and his physical struggle to complete a 22-day piece, Restivo creates fleeting moments of intimacy in the town's first known work of performance art.

The aim of this paper is to present results from the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Continuous Update Project on colorectal cancer and food, nutrition, and physical activity, an updated systematic literature review on evidence forming part of the 2007 WCRF/AICR Second Expert Report. Convincing evidence indicates that physical activity protects against colon cancer and that foods containing dietary fiber protect against colorectal cancer. Consumption of red meat and processed meat, ethanol from alcoholic drinks (by men and probably by women), as well as body fatness and abdominal fatness and the factors that lead to greater adult-attained height or its consequences are convincing causes of colorectal cancer. Consumption of garlic, milk, and calcium probably protects against this cancer. The updated evidence shows that food, nutrition, and physical activity have an important role in the causation and prevention of colorectal cancer.

An outbreak of Salmonella enterica serotype Choleraesuis enteritis occurred in two juvenile goitered gazelles and an adult Malayan tapir over a period of 5 wk at the Minnesota Zoo. Diagnosis was made postmortem on one gazelle and one tapir, and a second gazelle was diagnosed via fecal culture. The death of the tapir was attributed to S. enterica serovar Choleraesuis septicemia, while salmonellosis was considered to be a contributing factor besides ostertagiasis for the death of one goitered gazelle and for the diarrhea of another goitered gazelle. A third gazelle became ill in the same time period, but Salmonella infection was not confirmed by culture. All exhibited the clinical signs of profuse, watery diarrhea. The gazelles developed a protein-losing enteropathy, and the tapir showed signs of sepsis and endotoxemia. Serotyping and pulsed-field gel electrophoresis revealed the Salmonella isolates to be indistinguishable from each other. One year prior to this outbreak, Salmonella sp. was cultured from a Visayan warty pig (Sus cebifrons) housed in the same building as the tapir. After further investigation into the outbreak, spread of this pathogen was speculated to be associated with human movement across animal areas.

Life story work has been promoted as a tool to enhance the care provided to older people, particularly those with dementia. The benefits for individuals, families and/or friends and for staff include improving understanding of the individual, promoting relationships and assisting in the delivery of person-centred care. However, professionals often experience difficulties using life story work. This article considers a range of life story tools and advice on gathering information about a person. It highlights the importance of leadership and developing positive cultures to ensure that life story work can be effectively sustained.

Background: Declining fertility rates are often attributed to lack of interest in having children by new generations of men and women. However, the extent to which fertility decline is the result of entirely unconstrained personal choice is open to question. While there is a growing body of research demonstrating that young women continue to value having children, young men’s perspectives remain relatively unexamined. Objective: This article aimed to contribute to understanding of contemporary fertility trends by investigating the reproductive attitudes and preferences of young adult men. Methods: 399 single, childless, Australian men aged 18–25 years completed a survey which measured their desired number of children, personal importance of fatherhood and identified reasons for and against having a child. An open‐ended question also assessed participants’ perceptions of the fatherhood role in the context of their future lives. Results: The overwhelming majority of men (96%) wanted to have children, and th...

Background and objective: The assessment of chronic cough has been improved by the development of objective ambulatory cough monitoring systems and subjective quality of life questionnaires. Experimental induction of cough is a useful tool in the assessment of the cough reflex. We wanted to assess the reproducibility of and association between these measurements. Methods: This was a prospective observational study in patients with chronic cough of greater than 6 months' duration. All patients had an initial 24-h cough recording. They also completed a Leicester Cough Questionnaire, a Symptom Assessment Score, a Visual Analogue Score for cough and had a capsaicin cough challenge performed. They were reviewed at 8 weeks when all assessments were repeated. Results: Twenty-five patients (15 women) with a mean age of 54 years were included in the study. The median cough count at the second visit (302) was significantly lower compared to the first visit (381, P

This article provides an overview of factors relevant to dementia care today. The number of people experiencing dementia is increasing and dementia is at the forefront of health policy. The evidence base for person-centred approaches and interventions in dementia is expanding and nurses are central to implementing these across care settings. This is an exciting and challenging time for dementia care and nursing has a major role in leading and developing these changes in practice. The article discusses the importance of wellbeing and the Mental Capacity Act in assessing and caring for people with dementia. Psychosocial and pharmacological approaches to dementia care are described and the need to support carers of people with dementia is emphasised.

Introduction A baby’s size and shape at birth depends on how well they grow in the womb.Within the usual range,heavier and longer babies tend to become taller children and adults.A baby’s birthweight and an adult’s height both reflect a complex interplay of genetics,nutrition and other environmental factors that affect growth within the womb and during childhood and adolescence.While global cancer burden is constantly rising, there has been a growing research interest in the links between birthweight, adult attained height and cancer.This talk will present the latest global evidence from the World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) Third Expert Report (2018) on height,birthweight and the risk of cancer and will suggest future research directions. Material and methods The Third Expert Report provides a comprehensive analysis,using the most meticulous of methods,of the worldwide body of evidence on preventing and surviving cancer through diet, nutrition and physical activity.Dose-response meta-analyses of cohort studies on height as well as on birthweight and the risk of cancer were conducted using the increment of 5 cm on height and 500 g on birthweight.The accumulated,global evidence was independently assessed by a panel of international scientists to draw conclusions about which factors increase or decrease the risk of developing cancer. Results and discussions The risk of several adult cancers varies with markers of aspects of growth and development in early life.While neither birthweight nor height is likely to affect the risk of cancer directly,there is strong evidence that developmental factors leading to greater growth in length in childhood (marked by adult attained height) increase the risk of pancreas,colorectum,breast(pre and postmenopausal), ovary,endometrium,prostate, kidney and skin (malignant melanoma).For example,the RR (95% CI) per 5 cm increase in height is 1.07 (1.03–1.12),1.08 (1.05–1.10)and 1.10 (1.08–1.12) for pancreas,ovary and kidney cancer respectively.Additionally,factors that lead to a greater birthweight increase the risk of premenopausal breast cancer [RR (95% CI)=1.05 (1.02–1.09),based upon 16 studies, n>3135]. Conclusion As evidence accrues,it is clear that nutritional factors are key determinants of patterns of growth from preconception to completion of growth affecting the susceptibility to cancer later in life.Further research is needed to determine the precise mechanisms through which factors may influence growth and development and their relation to cancer risk.