Is there enough evidence with evolocumab and alirocumab (antibodies to proprotein convertase substilisin-kexin type, PCSK9) on cardiovascular outcomes to use them widely?

Introduction: Statins alone often do not reduce LDL cholesterol levels sufficiently to given maximum cardiovascular benefit. Thus, additional drugs are required to reduce the levels of LDL cholesterol. Monoclonal antibodies to PCSK9 have recently been shown to decrease LDL cholesterol, but it is not known whether they improve cardiovascular outcomes. Areas covered: Evaluation of two clinical trials reporting cardiovascular outcomes with antibodies to PCSK9; the OSLER extension with evolocumab and the ODYSSEY LONG TERM trial with alirocumab. Expert opinion: In OSLER and ODYSSEY LONG TERM, there were very few cardiovascular outcomes, but the trials do suggest that evolocumab and alirocumab may reduce these outcomes. However, there are also some safety concerns with both of these antibodies. Large clinical outcome trials are underway with both evolocumab and alirocumab, which will probably clarify both the safety concerns and any cardiovascular benefits with these antibodies. In our opinion, these antibodies may be suitable for use in subjects with familial hypercholesterolemia, who are uncontrolled with their present medications, provided intensive safety and cardiovascular monitoring is being undertaken. However, evolocumab and alirocumab should be used with caution in other subjects, until outcome studies in higher numbers of subjects, have shown acceptable safety and cardiovascular profiles.

The development and preliminary testing of an instrument for assessing fatigue self-management outcomes in patients with advanced cancer

Background: Fatigue is one of the most distressing and commonly experienced symptoms in patients with advanced cancer. Although the self-management (SM) of cancer-related symptoms has received increasing attention, no research instrument assessing fatigue SM outcomes for patients with advanced cancer is available. Objectives: to describe the development and preliminary testing of an interviewer administered instrument for assessing the frequency, and perceived levels of effectiveness and self-efficacy associated with fatigue SM behaviors in patients with advanced cancer. Methods: The development and testing of the Self-efficacy in Managing Symptoms Scale- Fatigue Subscale for Patients with Advanced Cancer (SMSFS-A) involved a number of procedures: item-generation using a comprehensive literature review and semi-structured interviews, content validity evaluation using expert panel reviews, and face validity and test-retest reliability evaluation using pilot testing. Results: Initially, 23 items (22 specific behaviors with one global item) were generated from the literature review and semi-structured interviews. After two rounds of expert panel review, the final scale was reduced to 17 items (16 behaviors with one global item). Participants in the pilot test (n=10) confirmed that the questions in this scale were clear and easy to understand. Bland-Altman analysis showed agreement of results over a one-week interval. Conclusions: The SMSFS-A items were generated using multiple sources. This tool demonstrated preliminary validity and reliability. Implications for practice: The SMSFS-A has the potential to be used for clinical and research purposes. Nurses can use this instrument for collecting data to inform the initiation of appropriate fatigue SM support for this population.

Cord blood 25-hydroxyvitamin D and fetal growth in the China-Anhui birth cohort study

We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: −110.5, −26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration.

Cost and outcomes of assessing patients with chest pain in an Australian emergency department

Objectives: We sought to characterise the demographics, length of admission, final diagnoses, long-term outcome and costs associated with the population who presented to an Australian emergency department (ED) with symptoms of possible acute coronary syndrome (ACS). Design, setting and participants: Prospectively collected data on ED patients presenting with suspected ACS between November 2008 and February 2011 was used, including data on presentation and at 30 days after presentation. Information on patient disposition, length of stay and costs incurred was extracted from hospital administration records. Main outcome measures: Primary outcomes were mean and median cost and length of hospital stay. Secondary outcomes were diagnosis of ACS, other cardiovascular conditions or non-cardiovascular conditions within 30 days of presentation. Results: An ACS was diagnosed in 103 (11.1%) of the 926 patients recruited. 193 patients (20.8%) were diagnosed with other cardiovascular-related conditions and 622 patients (67.2%) had non-cardiac-related chest pain. ACS events occurred in 0 and 11 (1.9%) of the low-risk and intermediate-risk groups, respectively. Ninety-two (28.0%) of the 329 high-risk patients had an ACS event. Patients with a proven ACS, high-grade atrioventricular block, pulmonary embolism and other respiratory conditions had the longest length of stay. The mean cost was highest in the ACS group ($13 509; 95% CI, $11 794–$15 223) followed by other cardiovascular conditions ($7283; 95% CI, $6152–$8415) and non-cardiovascular conditions ($3331; 95% CI, $2976–$3685). Conclusions: Most ED patients with symptoms of possible ACS do not have a cardiac cause for their presentation. The current guideline-based process of assessment is lengthy, costly and consumes significant resources. Investigation of strategies to shorten this process or reduce the need for objective cardiac testing in patients at intermediate risk according to the National Heart Foundation and Cardiac Society of Australia and New Zealand guideline is required.

Daily manifestations of career adaptability: Relationships with job and career outcomes

Most research on career adaptability has examined the construct as an individual differences variable and neglected that it may vary within an individual over a short period of time. In two daily diary studies, the author investigated the relationships of career adaptability and its four dimensions (concern, control, curiosity, and confidence) to their daily manifestations as well as daily job and career outcomes. Both Study 1 (N = 53) and Study 2 (N = 234) demonstrated substantial within-person variability in employees' behavioral expressions of career adaptability across five work days. Results further showed that daily career adaptability and daily confidence positively predicted daily task and career performance, as well as daily job and career satisfaction. Daily control positively predicted daily task performance, as well as daily job and career satisfaction. Daily concern positively predicted daily career performance and satisfaction, and daily curiosity positively predicted daily career satisfaction.

Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: Systematic review and meta-analysis

Objective To assess the impact of exercise referral schemes on physical activity and health outcomes. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, Cochrane Library, ISI Web of Science, SPORTDiscus, and ongoing trial registries up to October 2009. We also checked study references. Study selection - Design: randomised controlled trials or non-randomised controlled (cluster or individual) studies published in peer review journals. - Population: sedentary individuals with or without medical diagnosis. - Exercise referral schemes defined as: clear referrals by primary care professionals to third party service providers to increase physical activity or exercise, physical activity or exercise programmes tailored to individuals, and initial assessment and monitoring throughout programmes. - Comparators: usual care, no intervention, or alternative exercise referral schemes. Results Eight randomised controlled trials met the inclusion criteria, comparing exercise referral schemes with usual care (six trials), alternative physical activity intervention (two), and an exercise referral scheme plus a self determination theory intervention (one). Compared with usual care, follow-up data for exercise referral schemes showed an increased number of participants who achieved 90-150 minutes of physical activity of at least moderate intensity per week (pooled relative risk 1.16, 95% confidence intervals 1.03 to 1.30) and a reduced level of depression (pooled standardised mean difference −0.82, −1.28 to −0.35). Evidence of a between group difference in physical activity of moderate or vigorous intensity or in other health outcomes was inconsistent at follow-up. We did not find any difference in outcomes between exercise referral schemes and the other two comparator groups. None of the included trials separately reported outcomes in individuals with specific medical diagnoses. Substantial heterogeneity in the quality and nature of the exercise referral schemes across studies might have contributed to the inconsistency in outcome findings. Conclusions Considerable uncertainty remains as to the effectiveness of exercise referral schemes for increasing physical activity, fitness, or health indicators, or whether they are an efficient use of resources for sedentary people with or without a medical diagnosis.

Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study

Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: A case study for technology appraisal on the basis of surrogate outcomes evidence

Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence’s recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21–23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).

Republished research: Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: systematic review and meta-analysis

Study question Can exercise referral schemes improve health outcomes in individuals with or without pre-existing conditions? Summary answer We found weak evidence of a short term increase in physical activity and reduction in levels of depression in sedentary individuals after participation in exercise referral schemes, compared with after usual care. What is known and what this paper adds Exercise referral schemes are commonly used in primary care to promote physical activity. Evidence indicating a health benefit of these schemes is limited, so their value in primary care remains to be ascertained.

Designing rich information experiences to shape learning outcomes

Students in higher education typically learn to use information as part of their course of study, which is intended to support ongoing academic, personal and professional growth. Informing the development of effective information literacy education, this research uses a phenomenographic approach to investigate the experiences of a teacher and students engaged in lessons focused on exploring language and gender topics by tracing and analyzing their evolution through scholarly discourse. The findings suggest that the way learners use information influences content-focused learning outcomes, and reveal how teachers may enact lessons that enable students to learn to use information in ways that foster a specific understanding of the topic they are investigating.

A systematic review of studies identifying predictors of poor return to work outcomes following workplace injury

BACKGROUND: Injuries occurring in the workplace can have serious implications for the health of the individual, the productivity of the employer and the overall economic community. OBJECTIVE: The objective of this paper is to increase the current state of understanding of individual demographic and psychosocial characteristics associated with extended absenteeism from the workforce due to a workplace injury. METHODS: Studies included in this systematic literature review tracked participants' return to work status over a minimum of three months, identified either demographic, psychosocial or general injury predictors of poor return to work outcomes and included a heterogeneous sample of workplace injuries. RESULTS: Identified predictors of poor return to work outcomes included older age, female gender, divorced marital status, two or more dependent family members, lower education levels, employment variables associated with reduced labour market desirability, severity or sensitive injury locations, negative attitudes and outcome perceptions of the participant. CONCLUSIONS: There is a need for clear and consistent definition and measurement of return to work outcomes and a holistic theoretical model integrating injury, psychosocial and demographic predictors of return to work. Through greater understanding of the nature of factors affecting return to work, improved outcomes could be achieved.

Placental infection with Ureaplasma species is associated with histologic chorioamnionitis and adverse outcomes in moderately preterm and late-preterm infants

Objective The human Ureaplasma species are the microbes most frequently isolated from placentae of women who deliver preterm. The role of Ureaplasma species has been investigated in pregnancies at <32 weeks of gestation, but currently no studies have determined the prevalence of ureaplasmas in moderately preterm and late-preterm (hereafter, “moderate/late preterm”) infants, the largest cohort of preterm infants. Methods Women delivering moderate/late preterm infants (n = 477) and their infants/placentae (n = 535) were recruited, and swab specimens of chorioamnion tissue, chorioamnion tissue specimens, and cord blood specimens were obtained at delivery. Swab and tissue specimens were cultured and analyzed by 16S ribosomal RNA polymerase chain reaction (PCR) for the presence of microorganisms, while cord blood specimens were analyzed for the presence of cytokines, chemokines, and growth factors. Results We detected microorganisms in 10.6% of 535 placentae (443 were delivered late preterm and 92 were delivered at term). Significantly, Ureaplasma species were the most prevalent microorganisms, and their presence alone was associated with histologically confirmed chorioamnionitis in moderate/late preterm and term placentae (P < .001). The presence of ureaplasmas in the chorioamnion was also associated with elevated levels of granulocyte colony-stimulating factor (P = .02). Conclusions These findings have important implications for infection and adverse pregnancy outcomes throughout gestation and should be of major consideration for obstetricians and neonatologists.

When did you last predict a good idea? Exploring the case of assessing creativity through learning outcomes

It has been noted elsewhere that an idea is acknowledged to be creative if it is novel, or surprising and adaptive. So how does that fit with education's desire to measure student performance against fixed, consistent and predicted learning outcomes? This study explores practical measures and theoretical constructs that address the dearth of teaching, learning and assessment strategies to enhance creative capacity in enterprise and entrepreneurship education. It is argued that inappropriate assessment strategies can be significant inhibitors of the creativity of students and teachers. Referring to the broader discipline of 'design', as defined by Bruce and Besant (2002) – the application of human creativity to a purpose – both broad employer satisfaction with education and fast growing economic success are found (DCMS, 2014). As predictable assessment outcomes equal predictable students, these understandings can inform educators who wish to map and develop enhanced creative endeavours such as opportunity recognition, communication and innovation.

End-of-life care pathways for improving outcomes in caring for the dying

This is an updated version of a Cochrane review published in Issue 11, 2013 in the Cochrane Library. In many clinical areas, integrated care pathways are utilised as structured multidisciplinary care plans that detail essential steps in caring for patients with specific clinical problems. In particular, care pathways for the dying have been developed as a model to improve care of patients who are in the last days of life. The care pathways were designed with an aim of ensuring that the most appropriate management occurs at the most appropriate time, and that it is provided by the most appropriate health professional. Since the last update, there have been sustained concerns about the safety of implementing end-of-life care pathways, particularly in the United Kingdom (UK). Therefore, there is a significant need for clinicians and policy makers to be informed about the effects of end-of-life care pathways via a systematic review.

Child dietary and eating behaviour outcomes up to 3.5 years after an early feeding intervention: the NOURISH RCT

- Objective To evaluate dietary intake impact outcomes up to 3.5 years after the NOURISH early feeding intervention (concealed allocation, assessor masked RCT). - Methods 698 first-time mothers with healthy term infants were allocated to receive anticipatory guidance on protective feeding practices or usual care. Outcomes were assessed at 2, 3.7 and 5 years (3.5 years post-intervention). Dietary intake was assessed by 24-hour recall and Child Dietary Questionnaire. Mothers completed a food preference questionnaire and Children’s Eating Behaviour Questionnaire. Linear mixed models assessed group, time and time x group effects. - Results There were no group or time x group effects for fruit, vegetables, discretionary food and non-milk sweetened beverages intake. Intervention children showed a higher preference for fruits (74.6% vs 69.0% liked, P<.001), higher Child Dietary Questionnaire score for fruit and vegetables (15.3 vs 14.5, target>18, P=0.03), lower food responsiveness (2.3 vs 2.4, of maximum 5, P=.04) and higher satiety responsiveness (3.1 vs 3.0, of maximum 5, P=.04). - Conclusions Compared to usual care, an early feeding intervention providing anticipatory guidance regarding positive feeding practices led to small improvements in child dietary score, food preferences and eating behaviours up to 5 years of age, but not in dietary intake measured by 24-hour recall.