Purpose
ConquerFear is an efficacious intervention for fear of cancer recurrence (FCR) that demonstrated greater improvements than an attention control (relaxation training) in a randomized ...controlled trial. This study aimed to determine mediators and moderators of the relative treatment efficacy of ConquerFear versus relaxation.
Methods
One hundred and fifty-two cancer survivors completed 5 therapy sessions and outcome measures before and after intervention and at 6 months’ follow-up. We examined theoretically relevant variables as potential mediators and moderators of treatment outcome. We hypothesized that metacognitions and intrusions would moderate and mediate the relationship between treatment group and FCR level at follow-up.
Results
Only total FCR score at baseline moderated treatment outcome. Participants with higher levels of FCR benefited more from ConquerFear relative to relaxation on the primary outcome. Changes in metacognitions and intrusive thoughts about cancer during treatment partially mediated the relationship between treatment group and FCR.
Conclusions
These results show that ConquerFear is relatively more effective than relaxation for those with overall higher levels of FCR. The mediation analyses confirmed that the most likely mechanism of treatment efficacy was the reduction in unhelpful metacognitions and intrusive thoughts during treatment, consistent with the theoretical framework underpinning ConquerFear.
Implications for Cancer Survivors
ConquerFear is a brief, effective treatment for FCR in cancer survivors with early-stage disease. The treatment works by reducing intrusive thoughts about cancer and changing beliefs about worry and is particularly helpful for people with moderate to severe FCR.
IntroductionCardiac disease in pregnancy remains the leading cause of mortality and morbidly worldwide. Recognition and management can be challenging. In response to the MBRRACE Confidential Equiry ...into Maternal Deaths (Knight et al. 2016), we developed an interprofessional simulation-based training programme; 50% practical/technical skills and 50% human-factors skills.Summary of workA day long, high fidelity simulation course was designed and delivered on 6 occasions with plans to deliver it again.Each scenario involved a simulated-patient, played by the Maternal Simulator (Noelle®), an embedded practitioner and course participants (3–5) comprising of midwives, obstetricians, physicians and anaesthetists. Scenarios included acute coronary syndrome, pulmonary oedema, aortic dissection and cardiac arrest requiring peri-mortem C-section and were designed to meet a learning needs analysis associated with the outcomes of MBRRACE. Scenarios were followed by a debrief using the SaIL Diamond Debrief.The learning aims wereKnowing and understanding the symptoms, signs and management of cardiac disease in pregnancy, utilising a systematic ABCDEF approach and develop human factor skill to improve patient.The impact of training was measured using a pre and post intervention assessment with a validated and reliable to tool for assessing interprofessional learning in human factor skills (Reedy et al. 2017) and participants knowledge of clinical management of cardiac disease in pregnancy.ResultsThe intervention was delivered to 84 interprofessional healthcare professionals. There was an improvement in both participants’ knowledge, clinical management of cardiac disease in pregnancy and an improvement in a validated and reliable self-efficacy human-factors toolkit;I am confident in my knowledge of the physiological changes of the heart in pregnancy. The chi–square statistic was 15.4189. The p–value was <0.0001.I am confident in managing pregnant women with cardiac disease. The chi–square statistic was 15.4756. The p–value was <0.0001.Using the Human Factor Skills for Healthcare Instrument 0–10 score. The paired two–tailed T–test of 42 sets of paired pre and post data had a mean change 0.96. The value of t was 6.854051. The p–value was <0.00001.DiscussionThis interprofessional high fidelity course aimed to reduce mortality associated with cardiac morbidity. It addressed nationally identified learning needs in obstetric medicine. Through validated methodology, there is a demonstrable increased in human factor skills and technical knowledge and confidence in managing cardiac disease, whilst allowing for a greater understanding of others’ professional roles. Future work aims to demonstrate an enduring impact on practice.ReferencesKnight M, Nair M, Tuffnell D, Kenyon S, Shakespeare J, Brocklehurst P, Kurinczuk JJ (Eds.) on behalf of MBRRACE-UK. Saving Lives, Improving Mothers’ Care – Surveillance of maternal deaths in the UK 2012–2014 and lessons learned to inform maternity care from the UK and Ireland Con dential Enquiries into Maternal Deaths and Morbidity 2009–2014 2016. Oxford: National Perinatal Epidemiology Unit, University of Oxford.Reedy GB, Lavelle M, Simpson T, Anderson J. Development of the human factors skills for healthcare instrument: A valid and reliable tool for assessing interprofessional learning across healthcare practice settings. BMJ Simulation and Technology Enhanced Learning 2017;3(4):135–41.
The PPR Panel was asked to deliver a scientific opinion on the science behind the development of a risk assessment of plant protection products on bees (Apis mellifera, Bombus spp. and solitary ...bees). Specific protection goals options were suggested based on the ecosystem services approach. The different routes of exposure were analysed in detail for different categories of bees. The existing test guidelines were evaluated and suggestions for improvement and further research needs were listed. A simple prioritisation tool to assess cumulative effects of single pesticides using mortality data is suggested. Effects from repeated and simultanous exposure and synergism are discussed. Proposals for separate risk assessment schemes, one for honey bees and one for bumble bees and solitary bees, were developed.
In the Methods section of this Article, 'greater than' should have been 'less than' in the sentence 'Putative regions of clustered rearrangements were identified as having an average ...inter-rearrangement distance that was at least 10 times greater than the whole-genome average for the individual sample. '. The Article has not been corrected.
ObjectiveTo evaluate the safety and efficacy of zilucoplan in an interim analysis of RAISE-XT (NCT04225871). Collating long-term clinical data will contribute to an increased understanding of the ...safety profile of zilucoplan in generalized myasthenia gravis (gMG).MethodsRAISE-XT, a Phase 3, multicenter, open-label extension study, recruited patients with gMG who participated in randomized Phase 2 (NCT03315130) and Phase 3 (NCT04115293) zilucoplan studies. All patients self-administered daily subcutaneous injections of 0.3 mg/kg zilucoplan. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). Key secondary outcomes included Myasthenia Gravis Activities of Daily Living (MG-ADL) score.Results199 patients enrolled in RAISE-XT; 104 continued zilucoplan from their qualifying study (zilucoplan group) and 95 switched to zilucoplan from placebo (placebo-switch group). Median exposure at data cut-off was 253.0 (range 29–765) days. 169 (84.9%) patients experienced a TEAE; 46 (23.1%) patients experienced a serious TEAE. Most common TEAEs were headache and worsening of MG, both in 33 (16.6%) patients. At extension study Week 12, after 24 weeks of zilucoplan, the zilucoplan group achieved a least square mean change in MG-ADL score from double-blind study baseline of −6.30 (95% CI: −7.44, −5.15). MG-ADL reduction from baseline for the placebo-switch group, after 12 weeks of zilucoplan, was −6.32 (95% CI: −8.00, −4.65).ConclusionIn this interim analysis of RAISE-XT, zilucoplan demonstrated a favorable long-term safety profile. Efficacy in patients who had previously received zilucoplan continued to improve and was demonstrated for those who switched from placebo. The study is ongoing. Funding: UCB Pharma.
Cardiac disease in pregnancy remains the leading cause of mortality and morbidly worldwide. Recognition and management can be challenging. In response, we developed a multi-disciplinary ...simulation-based training programme; 50% practical/technical skills and 50% human-factors/non-technical skills (communication, leadership and teamwork).
Utilising a systematic ABCDE approach, knowing & understanding the symptoms, signs & management of cardiac disease in pregnancy and be aware of the important human factors to improve patient safety.
Each scenario involved a simulated-patient, played by the Maternal Simulator (Noelle®), an embedded practitioner and course participants (3–5) comprising of midwives, obstetricians, physicians and anaesthetists. Scenarios included acute coronary syndrome, pulmonary oedema, aortic dissection and cardiac arrest.
This study evaluated the educational impact of six one-day courses with healthcare staff (n = 84). There was an improvement in both participants’ knowledge, clinical management of cardiac disease in pregnancy and an improvement in a validated and reliable self-efficacy human-factors toolkit;
I am confident in my knowledge of the physiological changes of the heart in pregnancy. The chi-square statistic was 15.4189. The p-value was <0.0001.
I am confident in managing pregnant women with cardiac disease. The chi-square statistic was 15.4756. The p-value was <0.0001.
Using the Human Factor Skills for Healthcare Instrument 0–10 score. The paired two-tailed T-test of 42 sets of paired pre and post data had a mean change 0.96. The value of t was 6.854051. The p-value was <0.00001.
This course provided technical knowledge and confidence in managing cardiac disease, whilst allowing for a greater understanding of others’ professional roles. Simulation-based education is a promising avenue for reducing the mortality and morbidity of cardiac disease in pregnancy. It is responsive to the changing needs of the team whilst managing a pregnant woman.
Alkaline phosphatase (AP) isozymes are present in a wide range of species from bacteria to man and are capable of dephosphorylation and transphosphorylation of a wide spectrum of substrates in vitro. ...In humans, four AP isozymes have been identified—one tissue-nonspecific (TNAP) and three tissue-specific—named according to the tissue of their predominant expression: intestinal (IAP), placental (PLAP) and germ cell (GCAP) APs. Modulation of activity of the different AP isozymes may have therapeutic implications in distinct diseases and cellular processes. For instance, changes in the level of IAP activity can affect gut mucosa tolerance to microbial invasion due to the ability of IAP to detoxify bacterial endotoxins, alter the absorption of fatty acids and affect ectopurinergic regulation of duodenal bicarbonate secretion. To identify isozyme selective modulators of the human and mouse IAPs, we developed a series of murine duodenal IAP (Akp3-encoded dIAP isozyme), human IAP (hIAP), PLAP, and TNAP assays. High throughput screening and subsequent SAR efforts generated a potent inhibitor of dIAP, ML260, with specificity for the Akp3-, compared to the Akp5- and Akp6-encoded mouse isozymes.
The European Food Safety Authority (EFSA) asked the Panel on Plant Protection Products and their Residues (PPR) to develop an opinion on approaches to evaluate the toxicological relevance of ...metabolites and degradates of pesticide active substances in dietary risk assessment. This opinion identifies the threshold of toxicological concern (TTC) concept as an appropriate screening tool. The TTC values for genotoxic and toxic compounds were found to be sufficiently conservative for chronic exposure, as a result of a validation study with a group of pesticides belonging to different chemical classes. Three critical steps were identified in the application of a TTC scheme: 1) the estimate of the level of the metabolite, 2) the evaluation of genotoxicity alerts and 3) the detection of neurotoxic metabolites. Tentative TTC values for acute exposure were established by the PPR Panel by analysis of the lowest 5 th percentiles of No Observed Adverse Effect Levels (NOAELs) used to establish the Acute Reference Doses (ARfD) for the EFSA pesticide data set. Assessment schemes for chronic and acute dietary risk assessment of pesticide metabolites, using the TTC approach and combined (Q)SAR and read across, are proposed. The opinion also proposes how the risk assessment of pesticide metabolites that are stereoisomers should be addressed due to isomer ratio changes reflected in the composition of metabolites. The approach is ready for use, but it is anticipated that on many occasions the outcome of the assessment scheme will be that further testing is needed to reach a firm conclusion on the toxicological relevance of the metabolite. However, the benefit of applying the approach is that it will allow prioritisation of metabolites for subsequent testing.
EFSA will develop a Guidance Document based on the results in this opinion.
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