Development of a suite of metrics and indicators for children's nursing using consensus methodology.

AIM AND OBJECTIVES: To develop a suite of metrics and indicators to measure the quality of children's nursing care processes. The objectives were to identify available metrics and indicators and to develop consensus on the metrics and indicators to be measured. BACKGROUND: The Office of Nursing and Midwifery Services Director, Health Service Executive, in Ireland established seven workstreams aligned to the following care areas: acute, older persons, children's, mental health, intellectual disability, public health nursing and midwifery. DESIGN: A comprehensive design included stakeholder consultation and a survey with embedded open-ended questions. METHODS: A two-round online Delphi survey was conducted to identify metrics to be measured in practice, followed by a two-round online Delphi survey to identify the associated indicators for these metrics. A face-to-face consensus meeting was held with key stakeholders to review the findings and build consensus on the final metrics and indicators for use. A STROBE checklist was completed. RESULTS: A suite of eight nursing quality care process metrics and 67 associated process indicators was developed for children's nursing. CONCLUSIONS: By creating a national suite of metrics and indicators, more robust measurement and monitoring of nursing care processes can be achieved. This will enable the provision of evidence for any local and/or national level changes to policy and practice to enhance care delivery. RELEVANCE TO CLINICAL PRACTICE: The roll-out of the metrics and indicators in clinical practice has commenced. This national suite of metrics and indicators will ensure that a robust system of measurement for improvement is in place to provide assurance to Directors of Nursing of the quality of nursing care being provided to children and their families. It supports the value of nursing sensitive data to inform change and improvement in healthcare delivery and to demonstrate the contribution of the nursing workforce to safe patient care.

How Beliefs About Bladder Dysfunction Among Health-Care Professionals Influence Clinical Practice Development: Perspectives of Allied Health Professionals, Nurses, and Managers.

BACKGROUND: Bladder dysfunction can affect up to 75% of people with multiple sclerosis (MS) on several important life domains. It is a multifaceted problem that remains underdiagnosed by health-care professionals. The aims of this study were to understand the perceptions of Irish health-care professionals regarding bladder dysfunction and to explore current service provision for people with MS. METHODS: Two focus groups, three dyadic interviews, and one semistructured interview with 14 health-care professionals lasting up to 90 minutes were audio-recorded. Participants included eight physiotherapists, two occupational therapists, three nurses, and one clinical case manager from acute and community settings. RESULTS: Thematic analysis of transcripts yielded two key themes. The first theme involves the underlying beliefs of health-care professionals, their clinical practice, and experiential knowledge in the model of clinical practice development in relation to bladder management. The second theme addresses the pivotal points in this model where change can be implemented to optimize bladder management. The first element of change encompasses the interaction between clinical practice and experiential knowledge of health-care professionals. The second element of change incorporates how acknowledgment of individual beliefs of health-care professionals can further inform clinical practice and experiential knowledge. CONCLUSIONS: These findings suggest that health-care professionals need to be aware of their beliefs in relation to bladder dysfunction. Examining these beliefs may influence how people with MS access health service provision for this disabling symptom. This type of reflexive practice may facilitate changes to existing perceptions and reduce the reluctance to discuss bladder symptoms.

Cohort Study Comparing the Berg Balance Scale and the Mini-BESTest in People Who Have Multiple Sclerosis and Are Ambulatory.

BACKGROUND: The Berg Balance Scale (BBS) is a balance measure commonly used for people with multiple sclerosis (MS). The Mini-BESTest is an alternative based on balance systems. OBJECTIVE: The study objective was to compare the BBS and the Mini-BESTest for sensitivity to change, likelihood ratios for walking aid use and falls, and associations with clinical variables in people who have MS and are ambulatory. DESIGN: This was a cohort study with measurements before and after exposure to 8 weeks of routine physical therapy intervention. METHODS: For 52 participants who had a primary diagnosis of MS and who were independently mobile, with or without an aid, demographic details and a history of falls and near falls were collected. Participants completed the Mini-BESTest, Multiple Sclerosis Impact Scale-29, Multiple Sclerosis Walking Scale-12, BBS, Modified Fatigue Impact Scale, and Six-Minute Walk Test. RESULTS: No participant started with a baseline Mini-BESTest maximum score of 28, whereas 38.5% (n=20) started with a baseline BBS maximum score of 56. Statistically significant changes in the Mini-BESTest score (X̅=5.31, SD=3.5) and the BBS score (X̅=1.4, SD=1.9) were demonstrated. Effect sizes for the Mini-BESTest and the BBS were 0.70 and 0.37, respectively; standard response means for the Mini-BESTest and the BBS were 1.52 and 0.74, respectively. Areas under the receiver operating characteristic curves for the Mini-BESTest and the BBS were 0.88 and 0.77, respectively, for detecting mobility device use and 0.88 and 0.75, respectively, for detecting self-reported near falls. The Mini-BESTest had a higher correlation for each secondary measure than did the BBS. LIMITATIONS: This study involved a sample of convenience; 61% of the participants did not use a walking aid. The order of testing was not randomized, and fall status was obtained through retrospective recall. CONCLUSIONS: The Mini-BESTest had a lower ceiling effect and higher values on responsiveness tests. These findings suggest that the Mini-BESTest may be better at detecting changes in balance in people who have MS, are ambulatory, and have relatively little walking disability.

What do people with MS want from a web-based resource to encourage increased physical activity behaviour?

PURPOSE: To investigate what people with multiple sclerosis (PwMS) want from a web-based resource that encourages physical activity (PA). METHODS: Three focus groups (n = 22) and 11 semi-structured interviews were conducted. The semi-structured interviews were conducted using Skype (audio only) or telephone. Interviews were audio-recorded, transcribed verbatim and the thematic analysis approach described by Braun and Clarke was performed. RESULTS: The themes from the data were: (1) Content - important information to include, (2) Presentation - varying format, different abilities, (3) Interactivity - build a sense of community and (4) Reach the Audience - let people know. Participants believed the web resource to be a good idea and suggested that the content of resource should include a focus on the knowledge of the benefits of being physically active. Illustrating the types of exercise in which PwMS could participate in was also discussed. Ensuring information was stratified by mobility level and that the resource was interactive, portraying a 'Sense of Community' and use of success stories, was also suggested by participants. CONCLUSIONS: The data suggest that PwMS want a variety of information from a variety of sources and that this information is to be both stratified and interactive. These results will be used to inform the development of the 'Activity Matters' website which will aim to enable PwMS to become more physically active. Implications for Rehabilitation People with multiple sclerosis (PwMS) want information on the benefits of being physically active in order to change physical inactivity behaviours. Offering PwMS a range of exercise options that can be stratified by mobility and physical activity levels may further enable them to become more physically active. Peer support and creating a sense of community are important components when aiming to motivate PwMS to become more physically active.

Bladder dysfunction and quality of life for people with multiple sclerosis.

PURPOSE: Bladder dysfunction affects 75% of people with multiple sclerosis (MS). People with MS are reluctant to seek treatment for this distressing symptom. This is the first-known study to explore in depth how bladder dysfunction interferes with quality of life for people with MS. METHODS: Nineteen individual semi-structured interviews were conducted (M = 8, F = 11). Participants had a definite diagnosis of MS, aged between 37 and 64 years and had at least one bladder dysfunction symptom. The audio-recorded interviews lasted up to 90 min and were transcribed verbatim. RESULTS: Thematic analysis within NVivo10 yielded two key themes: (1) Disruptions and loss and (2) ways of knowing. "Disruptions and Loss" explores how bladder dysfunction interrupted daily living activities and how this contributed to experiencing loss. "Ways of knowing" portrays the types of knowledge that existed around bladder dysfunction. Participants described using their experiential knowledge to self-manage bladder symptoms without advice from healthcare providers. CONCLUSIONS: Bladder dysfunction imposes major disruptions on daily life. People with MS attempt to self-manage their bladder symptoms, despite current barriers to navigating existing healthcare infrastructure. Understanding these barriers and the individual strategies employed by people with MS are the first steps in facilitating independent management of bladder dysfunction. Implications for Rehabilitation Each individual's experience of bladder dysfunction is unique. Healthcare professionals must be prepared to discuss all disruptions and losses associated with bladder dysfunction for people with MS. People with MS have a vast range of knowledge in relation to their own bladder symptoms and healthcare professionals need to explore their existing self-management strategies during assessment. People with MS and healthcare professionals need to be educated on the wider health implications relating to bladder dysfunction.

Tuberculosis microepidemics among dispersed migrants, Birmingham, UK, 2004-2013.

To determine if local transmission was responsible for rising tuberculosis incidence in a recently dispersed migrant community in Birmingham, UK, during 2004-2013, we conducted enhanced epidemiologic investigation of molecular clusters. This technique identified exact locations of social mixing and chains of apparent recent transmission, which can be helpful for directing resources.

Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.

The integrity of male germ cell genome is critical for the correct progression of spermatogenesis, successful fertilization, and proper development of the offspring. Several DNA repair pathways exist in male germ cells. However, unlike somatic cells, key components of such pathways remain largely unidentified. Gametogenetin (GGN) is a testis-enriched protein that has been shown to bind to the DNA repair protein FANCL via yeast-two-hybrid assays. This finding and its testis-enriched expression pattern raise the possibility that GGN plays a role in DNA repair during spermatogenesis. Herein we demonstrated that the largest isoform GGN1 interacted with components of DNA repair machinery in the mouse testis. In addition to FANCL, GGN1 interacted with the critical component of the Fanconi Anemia (FA) pathway FANCD2 and a downstream component of the BRCA pathway, BRCC36. To define the physiological function of GGN, we generated a Ggn null mouse line. A complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos. Moreover, pachytene spermatocytes of the Ggn heterozygous knockout mice showed an increased incidence of unrepaired DNA double strand breaks (DSBs). Together, our results suggest that GGN plays a role in male meiotic DSB repair and is absolutely required for the survival of pre-implantation embryos.

Tmem26 is dynamically expressed during palate and limb development but is not required for embryonic survival.

The Tmem26 gene encodes a novel protein that we have previously shown to be regulated by hedgehog signalling in the mouse limb. We now report that Tmem26 expression is spatially and temporally restricted in other regions of the mouse embryo, most notably the facial primordia. In particular, Tmem26 expression in the mesenchyme of the maxillary and nasal prominences is coincident with fusion of the primary palate. In the secondary palate, Tmem26 is expressed in the palatal shelves during their growth and fusion but is downregulated once fusion is complete. Expression was also detected at the midline of the expanding mandible and at the tips of the eyelids as they migrate across the cornea. Given the spatio-temporally restricted expression of Tmem26, we sought to uncover a functional role in embryonic development through targeted gene inactivation in the mouse. However, ubiquitous inactivation of Tmem26 led to no overt phenotype in the resulting embryos or adult mice, suggesting that TMEM26 function is dispensable for embryonic survival.

Sox7 and Sox17 are strain-specific modifiers of the lymphangiogenic defects caused by Sox18 dysfunction in mice.

Developmental defects caused by targeted gene inactivation in mice are commonly subject to strain-specific modifiers that modulate the severity of the phenotype. Although several genetic modifier loci have been mapped in mice, the gene(s) residing at these loci are mostly unidentified, and the molecular mechanisms of modifier action remain poorly understood. Mutations in Sox18 cause a variable phenotype in the human congenital syndrome hypotrichosis-lymphedema-telangiectasia, and the phenotype of Sox18-null mice varies from essentially normal to completely devoid of lymphatic vasculature and lethal, depending on the strain of the mice, suggesting a crucial role for strain-specific modifiers in this system. Here we show that two closely related Group F Sox factors, SOX7 and SOX17, are able to functionally substitute for SOX18 in vitro and in vivo. SOX7 and SOX17 are not normally expressed during lymphatic development, excluding a conventional redundancy mechanism. Instead, these genes are activated specifically in the absence of SOX18 function, and only in certain strains. Our studies identify Sox7 and Sox17 as modifiers of the Sox18 mutant phenotype, and reveal their mechanism of action as a novel mode of strain-specific compensatory upregulation.

Functional analysis of the SRY-KRAB interaction in mouse sex determination.

BACKGROUND INFORMATION: SRY (sex-determining region Y), the master regulator of male development in mammals, has been studied extensively for more than 17 years, but how the SRY protein triggers the chain of events leading to testis development remains unclear. SRY probably requires a partner protein to elicit its molecular function. KRAB-O, a novel protein containing a KRAB (Krüppel-associated box) domain only, was suggested recently as a candidate SRY partner. In order to investigate the possible role of KRAB-O in sex determination, we studied its expression and conducted functional assays of the SRY-KRAB interaction. RESULTS: More than 100 KRAB genes were found to be expressed in mouse developing gonads, including 19 transcripts encoded by the KRAB-O cluster that were found to be expressed in somatic cells at 11.5 dpc (days post-coitum). Loss-of-function analysis in Sry-expressing cultured cells, using shRNA (small hairpin RNA) constructs directed against KRAB-O and its homologous genes, resulted in a reduced ability to up-regulate Sox9 [SRY-related HMG (high-mobility group)-box 9]; however, KRAB-knockdown mice exhibited normal testis development. CONCLUSIONS: Reduced Sox9 expression in KRAB-knockdown cells supports a role for KRAB-O and perhaps other KRAB genes in mediating SRY function. Overlapping expression and potential redundancy between members of the large KRAB-O gene cluster may mask any loss-of-function in vivo, presenting clear challenges for further functional analysis.

Sox18 induces development of the lymphatic vasculature in mice.

The lymphatic system plays a key role in tissue fluid regulation and tumour metastasis, and lymphatic defects underlie many pathological states including lymphoedema, lymphangiectasia, lymphangioma and lymphatic dysplasia. However, the origins of the lymphatic system in the embryo, and the mechanisms that direct growth of the network of lymphatic vessels, remain unclear. Lymphatic vessels are thought to arise from endothelial precursor cells budding from the cardinal vein under the influence of the lymphatic hallmark gene Prox1 (prospero homeobox 1; ref. 4). Defects in the transcription factor gene SOX18 (SRY (sex determining region Y) box 18) cause lymphatic dysfunction in the human syndrome hypotrichosis-lymphoedema-telangiectasia, suggesting that Sox18 may also play a role in lymphatic development or function. Here we use molecular, cellular and genetic assays in mice to show that Sox18 acts as a molecular switch to induce differentiation of lymphatic endothelial cells. Sox18 is expressed in a subset of cardinal vein cells that later co-express Prox1 and migrate to form lymphatic vessels. Sox18 directly activates Prox1 transcription by binding to its proximal promoter. Overexpression of Sox18 in blood vascular endothelial cells induces them to express Prox1 and other lymphatic endothelial markers, while Sox18-null embryos show a complete blockade of lymphatic endothelial cell differentiation from the cardinal vein. Our findings demonstrate a critical role for Sox18 in developmental lymphangiogenesis, and suggest new avenues to investigate for therapeutic management of human lymphangiopathies.

Genetic basis of human testicular germ cell cancer: insights from the fruitfly and mouse.

The prevalence of tumours of the germ line is increasing in the male population. This complex disease has a complex aetiology. We examine the contribution of genetic mutations to the development of germ line tumours in this review. In particular, we concentrate on fly and mouse experimental systems in order to demonstrate that mutations in some conserved genes cause pathologies typical of certain human germ cell tumours, whereas other mutations elicit phenotypes that are unique to the experimental model. Despite these experimental systems being imperfect, we show that they are useful models of human testicular germ cell tumourigenesis.