The development and cognitive testing of the positive outcomes HIV PROM: a brief novel patient-reported outcome measure for adults living with HIV.

BACKGROUND: People living with HIV experience burdensome multidimensional symptoms and concerns requiring person-centred care. Routine use of patient reported outcome measures can improve outcomes. There is no brief patient reported outcome measure (PROM) that currently reflects the breadth of concerns for people living with HIV. This study aimed to develop and cognitively test a brief novel patient reported outcome measure for use within routine adult HIV care- the "Positive Outcomes" HIV PROM. METHODS: Development followed the COSMIN taxonomy and guidance for relevance and comprehensiveness, and Rothrock guidance on development of valid patient reported outcome measures. The Positive Outcomes HIV PROM was developed by a steering group (people living with HIV, HIV professionals and health services researchers) using findings from a previously reported qualitative study of priority outcomes for people living with HIV. The prototype measure was cognitively tested with a purposive sample of people living with HIV. RESULTS: The Positive Outcomes HIV PROM consists of 23 questions (22 structured, and one open question) informed by the priorities of key stakeholders (n = 28 people living with HIV, n = 21 HIV professionals and n = 8 HIV commissioners) to ensure face and content validity, and refined through cognitive testing (n = 6 people living with HIV). Cognitive testing demonstrated high levels of acceptability and accessibility. CONCLUSIONS: The Positive Outcomes HIV PROM is the first brief patient reported outcome measure reflecting the diverse needs of people living with HIV designed specifically for use in the clinical setting to support patient assessment and care, and drive service quality improvement. It is derived from primary data on the priority outcomes for people living with HIV and is comprehensive and acceptable. Further psychometric testing is required to ensure reliability and responsiveness.

Towards person-centred care for people living with HIV: what core outcomes matter, and how might we assess them? A cross-national multi-centre qualitative study with key stakeholders.

OBJECTIVES: People living with HIV (PLWH) have multidimensional concerns requiring person-centred care. Routine use of patient-reported outcome measures (PROMs) improves outcomes. No brief PROM currently reflects the breadth of concerns for PLWH. This study sought to identify priority outcomes for PLWH, model current practice, explore views on introducing PROMs into routine care, and devise a model for person-centred care incorporating the PROM. METHODS: A cross-national multi-centre study (London, Brighton and Dublin) was carried out. Semi-structured qualitative interviews with adult PLWH, HIV health care professionals and HIV commissioners (responsible for planning and commissioning services) were performed. Interviews were analysed using thematic and framework analysis. RESULTS: PLWH (n = 28), professionals (n = 21) and commissioners (n = 8) described concerns related to living with HIV across six domains: physical (e.g. pain and gastrointestinal symptoms), cognitive (e.g. memory and sleep), psychological (e.g. anxiety and depression), social (e.g. isolation and intimacy), welfare (e.g. finances and fears regarding change of immigration status), and information (e.g. long-term outcomes) needs. Themes were highly inter-related, impacting across domains of need (e.g. physical and cognitive problems impacting on psychological and social wellbeing). Perceived benefits of using PROMs in routine HIV care included improved person-centredness, patient empowerment, fewer missed concerns, increased engagement with services, and informed planning of services. Potential challenges included heterogeneity of PLWH, literacy, and utility for those who struggle to engage with care. CONCLUSIONS: This study presents a novel model of person-centred care incorporating an HIV-specific PROM. The model reflects priorities of key stakeholders. Explicit use of PROMs in routine HIV care could afford benefits for PLWH, clinical teams and commissioners.

In vivo and in vitro models for the therapeutic targeting of Wnt signaling using a Tet-OΔN89ß-catenin system.

Although significant progress has been made in understanding the importance of Wnt signaling in the initiation of colorectal cancer, less is known about responses that accompany the reversal of oncogenic Wnt signaling. The aim of this study was to analyze in vivo and in vitro responses to an 'ideal' Wnt pathway inhibitor as a model for the therapeutic targeting of the pathway. A tetracycline-inducible transgenic mouse model expressing truncated ß-catenin (ΔN89ß-catenin) that exhibited a strong intestinal hyperplasia was analyzed during the removal of oncogenic ß-catenin expression both in 3D 'crypt culture' and in vivo. Oncogenic Wnt signaling was rapidly and completely reversed. The strongest inhibition of Wnt target gene expression occurred within 24 h of doxycycline removal at which time the target genes Ascl2, Axin2 and C-myc were downregulated to levels below that in the control intestine. In vitro, the small molecule Wnt inhibitor CCT036477 induced a response within 4 h of treatment. By 7 days following doxycycline withdrawal, gene expression, cell proliferation and tissue morphology were undistinguishable from control animals.In conclusion, these results demonstrate that the reversal of Wnt signaling by inhibitors should ideally be studied within hours of treatment. The reversible system described, involving medium throughput in vitro approaches and rapid in vivo responses, should allow the rapid advance of early stage compounds into efficacy models that are more usually considered later in the drug discovery pipeline.

How effective is amniotomy as a means of induction of labour?

BACKGROUND: Amniotomy or artificial rupture of membranes is routinely used for induction of labour. AIMS: To assess the efficacy of amniotomy alone for induction. METHODS: A retrospective descriptive study of 3,586 cases of amniotomy for induction of labour between July 1996 and December 1999. RESULTS: In total, 26,670 women delivered in the National Maternity Hospital during the study period. Of these 4,928 women required induction of labour and 72.8% of these (n = 3,586) underwent amniotomy only for induction of labour. Spontaneous labour occurred in 90.1% of the women who underwent amniotomy within 24 h. Oxytocin as an induction agent was employed in 9.8% of cases. Overall, 80.5% of the women had a spontaneous delivery, 7.3% had a ventouse delivery, 4.3% had a forceps delivery, and 7.9% underwent a caesarean section. In total, 90.5% of multips and 63.4% of primips had a spontaneous vaginal delivery. CONCLUSIONS: Amniotomy is a simple, safe and effective method of induction of labour.

Activation of mixed glia by Abeta-specific Th1 and Th17 cells and its regulation by Th2 cells.

Microglia are innate immune cells of the CNS, that act as antigen-presenting cells (APC) for antigen-specific T cells and respond to inflammatory stimuli, such as amyloid-beta (Abeta), resulting in the release of neurotoxic factors and pro-inflammatory cytokines. Astrocytes can also act as APC and modulate the function of microglia. However, the role of distinct T cell subtypes, in particular Th17 cells, in glial activation and subsequent modulatory effects of Th2 cells are poorly understood. Here, we generated Abeta-specific Th1, Th2, and Th17 cells and examined their role in modulating Abeta-induced activation of microglia in a mixed glial culture, a preparation which mimics the complex APC types in the brain. We demonstrated that mixed glia acted as an effective APC for Abeta-specific Th1 and Th17 cells. Addition of Abeta-specific Th2 cells suppressed the Abeta-induced IFN-gamma production by Th1 cells and IL-17 production by Th17 cells with glia as the APC. Co-culture of Abeta-specific Th1 or Th17 cells with glia markedly enhanced Abeta-induced pro-inflammatory cytokine production and expression of MHC class II and co-stimulatory molecules on the microglia. Addition of Abeta-specific Th2 cells inhibited Th17 cell-induced IL-1beta and IL-6 production by mixed glia and attenuated Th1 cell-induced CD86 and CD40 expression on microglia. The modest enhancement of MHC class II and CD86 expression on astrocytes by Abeta-specific Th1 and Th17 was not attenuated by Th2 cells. These data indicate that Abeta-specific Th1 and Th17 cells induce inflammatory activation of glia, and that this is in part regulated by Th2 cells.

Continuous renal replacement therapy in patients following traumatic injury.

In critically injured patients, the incidence of acute renal failure has been reported to occur in as many as 31% of patients. The use of CRRT modalities for patients following traumatic injuries is becoming more common, albeit slowly, and this therapy may impact upon long-term recovery of renal function and mortality. Historical studies investigating the early use of intermittent dialysis reported significant improvement in survival in patients who were dialyzed earlier and more vigorously than in control subjects. Early trauma patients also showed improved survival following war injuries when dialyzed prophylactically. Although there is a growing acceptance in favor of earlier renal replacement therapy, the published consensus and the practice in many centers has been to dialyze/filter relatively ill rather than relatively healthy patients. The R Adams Cowley Shock Trauma Center (STC) in Baltimore, Maryland, USA, admits over 8,000 trauma patients each year. Within the STC, a program of continuous renal replacement therapy was established in the early 1980's. We review both historical and current literature on the use of renal replacement therapies after traumatic injury, and suggest some future areas of investigation and indications for these modalities.

Influence of persistent occiput posterior position on delivery outcome.

OBJECTIVE: To evaluate the influence of intrapartum persistent occiput posterior position of the fetal head on delivery outcome and anal sphincter injury, with reference to the association with epidural analgesia. METHODS: We conducted a prospective observational study of 246 women with persistent occiput posterior position in labor during a 2-year period, compared with 13,543 contemporaneous vaginal deliveries with occiput anterior position. RESULTS: The incidence of persistent occiput posterior position was significantly greater among primiparas (2.4%) than multiparas (1.3%; P <.001; 95% confidence interval 1.4, 2.4) and was associated with significantly higher incidences of prolonged pregnancy, induction of labor, oxytocin augmentation of labor, epidural use, and prolonged labor. Only 29% of primiparas and 55% of multiparas with persistent occiput posterior position achieved spontaneous vaginal delivery, and the malposition was associated with 12% of all cesarean deliveries performed because of dystocia. Persistent occiput posterior position was also associated with a sevenfold higher incidence of anal sphincter disruption. Despite a high overall incidence of use of epidural analgesia (47% versus 3%), the institutional incidence of persistent occiput posterior position was lower than that reported 25 years ago. CONCLUSION: Persistent occiput posterior position contributed disproportionately to cesarean and instrumental delivery, with fewer than half of the occiput posterior labors ending in spontaneous delivery and the position accounting for 12% of all cesarean deliveries for dystocia. Persistent occiput posterior position leads to a sevenfold increase in the incidence of anal sphincter injury. Use of epidural analgesia was not related to the malposition.

Labour ward activity and the lunar cycle.

To refute the commonly held belief by the general public that the lunar cycle affects labour, we studied 10 027 deliveries over an 18-month period in a large maternity unit in Ireland. There was no increase in the total number of deliveries during the times of a full moon compared with other times. The caesarean section, instrumental vaginal delivery, and pre-term delivery rate remained unchanged over the times of a full moon. We conclude that the lunar cycle has no influence on labour ward activity.

Intracranial pressure monitoring: technical imperatives.

Intracranial pressure (ICP) monitoring provides extremely important information that is helpful in detecting intracranial hypertension and guiding therapeutic interventions that attempt to control this pathologic condition. This article reviews the purpose and rationale for monitoring ICP. Commonly used ICP monitoring systems are described, including their advantages, limitations, and nursing implications. This article also explains how to interpret ICP, ICP waveforms, and cerebral perfusion pressure. In addition, it addresses the application of data retrieved from ICP monitoring to clinical nursing practice and implications for nursing research.

Positioning as a nursing therapy in trauma care.

The therapy of patient positioning is an independent nursing intervention with profound implications for improving the outcomes of trauma patients. With knowledge of disease pathophysiology and the effects of position variations, the nurse can use available assessment parameters to guide positioning choices to optimize the patient's condition. Undoubtedly, further nursing research exploring the effects of positioning on pulmonary and cerebrovascular status is necessary to enhance the scientific basis for this nursing therapy.

Moving to the city: migration to London and Paris in the nineteenth century.

PIP: Rural-urban migration in England and France during the Industrial Revolution is examined. In particular, the author investigates factors underlying variations in rates of migration to London and Paris and concludes that the extent of change in migration patterns has been overestimated. Most migration continued to come from the hinterlands of the two cities and from other traditional sources, as the negative impact of distance overwhelmed other factors associated with regional variations.^ieng