End-of-life care (EoLC) communication skills training for generalist palliative care providers is recommended in policy guidance globally. Although many training programs now exist, there has been no ...comprehensive evidence synthesis to inform future training delivery and evaluation.
To identify and appraise how EoLC communication skills training interventions for generalist palliative care providers are developed, delivered, evaluated, and reported.
Systematic review. Ten electronic databases (inception to December 2015) and five relevant journals (January 2004 to December 2015) were searched. Studies testing the effectiveness of EoLC communication skills training for generalists were included. Two independent authors assessed study quality. Descriptive statistics and narrative synthesis are used to summarize the findings.
From 11,441 unique records, 170 reports were identified (157 published, 13 unpublished), representing 160 evaluation studies of 153 training interventions. Of published papers, eight were of low quality, 108 medium, and 41 high. Few interventions were developed with service user involvement (n = 7), and most were taught using a mixture of didactics (n = 123), reflection and discussion (n = 105), and role play (n = 86). Evaluation designs were weak: <30% were controlled, <15% randomized participants. Over half (n = 85) relied on staff self-reported outcomes to assess effectiveness, and 49% did not cite psychometrically validated measures. Key information (e.g., training duration, participant flow) was poorly reported.
Despite a proliferation of EoLC communication skills training interventions in the literature, evidence is limited by poor reporting and weak methodology. Based on our findings, we present a CONSORT statement supplement to improve future reporting and encourage more rigorous testing.
Background Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised ...comparison of the 3 interventions. The SuPPoRT “Stitch, Pessary, or Progesterone Randomised Trial” was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy. Methods and findings SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14 +0 and 23 +6 weeks’ gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage ( n = 128), cervical pessary ( n = 126), or vaginal progesterone ( n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks’ gestation. Secondary outcomes included PTB <34 weeks’, <30 weeks’, and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14 +0 and 23 +6 weeks’ gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) −0.7% −12.1 to 10.7, cerclage versus progesterone RD 6.2% −5.0 to 17.0, and progesterone versus pessary RD −6.9% −17.9 to 4.1). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic. Conclusions In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapies would be reasonable clinical management. These results can be used as a counselling tool for clinicians when managing women with a short cervix. Trial registration EU Clinical Trials register. EudraCT Number: 2015-000456-15, clinicaltrialsregister.eu., ISRCTN Registry: ISRCTN13364447 , isrctn.com .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There are significant knowledge gaps regarding the effectiveness of serial prophylactic exchange blood transfusion (SPEBT) for pregnant women with sickle cell disease (SCD). The protocol for the ...randomised feasibility trial assessing SPEBT versus usual care in women with SCD (TAPS2 trial) has previously been published. This publication outlines the statistical and qualitative analysis plan for the study.
TAPS2 is a randomised two-arm phase 2 feasibility trial with a nested qualitative study and health economic evaluation. Up to 50 pregnant women with SCD and a singleton pregnancy will be recruited and individually randomised to either SPEBT approximately every 6-10 weeks until delivery (intervention arm) or to usual care (control arm). Information will be collected on a range of feasibility and clinical outcomes.
Due to the impact of COVID-19 on study recruitment, the initial study period of 24 months was extended to 48 months. Other protocol updates designed to mitigate the impact of COVID-19-related disruption included allowing for remote consent and conducting all qualitative interviews by telephone. The primary outcome for the trial is the overall recruitment rate. The number of women screened, eligible, consented, randomised and withdrawn will be summarised as a CONSORT flow diagram. Differences in clinical outcomes will additionally be presented as an initial assessment of efficacy and to inform sample size calculations for a future definitive trial. Qualitative interviews with trial participants and clinicians will be analysed using reflexive thematic analysis; data from interviews with participants who declined to participate in the trial will be extracted and incorporated into summary tables to report key findings. The health economic analysis plan is not covered by this update.
The publication of this analysis plan is designed to aid transparency and to reduce the potential for reporting bias.
NIH registry ( www.
gov ), registration number NCT03975894 (registered 05/06/19); ISRCTN ( www.isrctn.com ), registration number ISRCTN52684446 (retrospectively registered 02/08/19).
Pregnancies in women with sickle cell disease (SCD) are associated with a higher risk of sickle and pregnancy complications. Limited options exist for treating SCD during pregnancy. Serial ...prophylactic exchange blood transfusion (SPEBT) has been shown to be effective in treating SCD outside pregnancy, but evidence is lacking regarding its use during pregnancy. The aim of this study is to assess the feasibility and acceptability of conducting a future phase 3 randomised controlled trial (RCT) to establish the clinical and cost effectiveness of SPEBT in pregnant women with SCD.
The study is an individually randomised, two-arm, feasibility trial with embedded qualitative and health economic studies. Fifty women, 18 years of age and older, with SCD and a singleton pregnancy at ≤ 18 weeks' gestation will be recruited from six hospitals in England. Randomisation will be conducted using a secure online database and minimised by centre, SCD genotype and maternal age. Women allocated to the intervention arm will receive SPEBT commencing at ≤ 18 weeks' gestation, performed using automated erythrocytapheresis every 6-10 weeks until the end of pregnancy, aiming to maintain HbS% or combined HbS/HbC% below 30%. Women in the standard care arm will only receive transfusion when clinically indicated. The primary outcome will be the recruitment rate. Additional endpoints include reasons for refusal to participate, attrition rate, protocol adherence, and maternal and neonatal outcomes. Women will be monitored throughout pregnancy to assess maternal, sickle, and foetal complications. Detailed information about adverse events (including hospital admission) and birth outcomes will be extracted from medical records and via interview at 6 weeks postpartum. An embedded qualitative study will consist of interviews with (a) 15-25 trial participants to assess experiences and acceptability, (b) 5-15 women who decline to participate to identify barriers to recruitment and (c) 15-20 clinical staff to explore fidelity and acceptability. A health economic study will inform a future cost effectiveness and cost-utility analysis.
This feasibility study aims to rigorously evaluate SPEBT as a treatment for SCD in pregnancy and its impact on maternal and infant outcomes.
NIH registry (www.clinicaltrials.gov), registration number NCT03975894 (registered 05/06/19); ISRCTN (www.isrctn.com), registration number ISRCTN52684446 (retrospectively registered 02/08/19).
UK policymakers, clinicians and public wish to see improvements in end-of-life care (EoLC). However, healthcare professionals' skills and knowledge to deliver high-quality care are often lacking. ...Since May 2012, palliative care staff in an inner-city tertiary hospital have run a 2-day Transforming End of Life Care (TEoLC) course to improve EoLC confidence, and competence among hospital and community staff.
To evaluate course participants' self-rated confidence, competence and knowledge of EoLC topics.
A before-and-after design using self-completion questionnaires, precourse and postcourse. 14 self-assessment questions examined confidence, understanding and knowledge of EoLC topics. Mean change scores and paired t tests were calculated and free-text responses analysed thematically.
236 staff members completed the course between May 2012 and April 2014. 42% worked in hospitals and 55% in the community; the most frequent staff roles were qualified nurses (49%), senior nurses (16%) and general practitioners (15%).
All 14 self-assessment topics improved significantly (p<0.001); most improved was 'understanding and implementing Fast Track discharge'. Qualitative data showed increased knowledge and confidence in EoLC, particularly in communication, commitment to team work and holistic care. Overall, 217 (92%) participants would recommend the course and 215 (98%) indicated it would influence their practice.
The TEoLC course improved participants' self-rated confidence, competence and knowledge in EoLC. Findings have utility beyond the UK in light of the international policy recommendations to improve the palliative care skills of generalist healthcare providers.
The restriction of intermingling between specific cell populations is crucial for the maintenance of organized patterns during development. A striking example is the restriction of cell mixing ...between segments in the insect epidermis and the vertebrate hindbrain that may enable each segment to maintain a distinctidentity. In the hindbrain, this is a result of different adhesive properties of odd- and even-numbered segments (rhombomeres),, but an adhesion molecule with alternating segmental expression has not been found. However, blocking experiments suggest that Eph-receptor tyrosine kinases may be required for the segmental restriction of cells. Eph receptors and their membrane-bound ligands, ephrins, are expressed in complementary rhombomeres and, by analogy with their roles in axon pathfinding,, could mediate cell repulsion at boundaries. Remarkably, transmembrane ephrins can themselves transduce signals,, raising the possibility that bi-directional signalling occurs between adjacent ephrin- and Eph-receptor-expressing cells. We report here that mosaic activation of Eph receptors leads to sorting of cells to boundaries in odd-numbered rhombomeres, whereas mosaic activation of ephrins results in sorting to boundaries in even-numbered rhombomeres. These data implicate Eph receptors and ephrins in the segmental restriction of cell intermingling.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: During vertebrate head development, neural crest cells migrate from hindbrain segments to specific branchial arches, where they differentiate into distinct patterns of skeletal ...structures. The rostrocaudal identity of branchial neural crest cells appears to be specified prior to migration, so it is important that they are targeted to the correct destination. In Xenopus embryos, branchial neural crest cells segregate into four streams that are adjacent during early stages of migration. It is not known what restricts the intermingling of these migrating cell populations and targets them to specific branchial arches. Here, we investigated the role of Eph receptors and ephrins – mediators of cell-contact-dependent interactions that have been implicated in neuronal pathfinding – in this targeted migration.
Results:Xenopus EphA4 and EphB1 are expressed in migrating neural crest cells and mesoderm of the third arch, and third plus fourth arches, respectively. The ephrin-B2 ligand, which interacts with these receptors, is expressed in the adjacent second arch neural crest and mesoderm. Using truncated receptors, we show that the inhibition of EphA4/EphB1 function leads to abnormal migration of third arch neural crest cells into second and fourth arch territories. Furthermore, ectopic activation of these receptors by overexpression of ephrin-B2 leads to scattering of third arch neural crest cells into adjacent regions. Similar disruptions occur when the expression of ephrin-B2 or truncated receptors is targeted to the neural crest.
Conclusions: These data indicate that the complementary expression of EphA4/EphB1 receptors and ephrin-B2 is involved in restricting the intermingling of third and second arch neural crest and in targeting third arch neural crest to the correct destination. Together with previous work showing that Eph receptors and ligands mediate neuronal growth cone repulsion, our findings suggest that similar mechanisms are used for neural crest and axon pathfinding.
The development of mAbs remains high on the therapeutic agenda for the majority of pharmaceutical and biotechnology companies. Often, the only relevant species for preclinical safety assessment of ...mAbs are non-human primates (NHPs), and this raises important scientific, ethical and economic issues. To investigate evidence-based opportunities to minimize the use of NHPs, an expert working group with representatives from leading pharmaceutical and biotechnology companies, contract research organizations and institutes from Europe and the USA, has shared and analyzed data on mAbs for a range of therapeutic areas. This information has been applied to hypothetical examples to recommend scientifically appropriate development pathways and study designs for a variety of potential mAbs. The addendum of ICHS6 provides a timely opportunity for the scientific and regulatory community to embrace strategies which minimize primate use and increase efficiency of mAb development.
The National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is an independent scientific organization that is based in the United Kingdom, which was set up by ...the government to lead the discovery and application of new technologies and approaches
that minimize the use of animals in research and improve animal welfare. The NC3Rs uses a range of strategies to improve and advance science through application of the 3Rs. These include funding basic research, open innovation (CRACK IT), and programs run by inhouse scientists. We present
several case studies from the NC3Rs portfolio, featuring asthma research, the use of nonhuman primates in monoclonal antibody development, and CRACK IT. Finally, we anticipate the future, as we use our experience to move into new research fields and expand toward international collaboration.
Here we highlight how equipping scientists with relevant and emerging 3Rs tools can help overcome the challenges and limitations of the use of animals in research to the benefit of the whole bioscience community.
As most end-of-life care is provided by health care providers who are generalists rather than specialists in palliative care, effective communication skills training for generalists is essential.
To ...determine the effect of communication training interventions for generalist palliative care providers on patient-reported outcomes and trainee behaviors.
Systematic review from searches of 10 databases to December 2015 (MEDLINE, EMBASE, PsycINFO, ERIC, CINAHL, CENTRAL, Web of Science, ICTRP, CORDIS, and OpenGrey) plus hand searching. Randomized controlled trials of training interventions intended to enhance generalists' communication skills in end-of-life care were included. Two authors independently assessed eligibility after screening, extracted data, and graded quality. Data were pooled for meta-analysis using a random-effects model. PRISMA guidelines were followed.
Nineteen of 11,441 articles were eligible, representing 14 trials. Eleven were included in meta-analyses (patients n = 3144, trainees n = 791). Meta-analysis showed no effect on patient outcomes (standardized mean difference SMD = 0.10, 95% CI −0.05 to 0.24) and high levels of heterogeneity (chi-square = 21.32, degrees of freedom df = 7, P = 0.003; I2 = 67%). The effect on trainee behaviors in simulated interactions (SMD = 0.50, 95% CI 0.19–0.81) was greater than in real patient interactions (SMD = 0.21, 95% CI −0.01 to 0.43) with moderate heterogeneity (chi-square = 8.90, df = 5, P = 0.11; I2 = 44%; chi-square = 5.96, df = 3, P = 0.11; I2 = 50%, respectively). Two interventions with medium effects on showing empathy in real patient interactions included personalized feedback on recorded interactions.
The effect of communication skills training for generalists on patient-reported outcomes remains unclear. Training can improve clinicians' ability to show empathy and discuss emotions, at least in simulated consultations. Personalized feedback on recorded patient interactions may be beneficial.
CRD42014014777.
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