Biological variation of CA 15-3, CA 125 and HE 4 on lithium heparinate plasma in apparently healthy Caucasian volunteers.

OBJECTIVES: Tumor markers are well-known for being important tools in the support of diagnosis, monitoring of treatment efficacy and follow-up of cancers. CA 125, CA 15-3 and HE 4 have demonstrated potential efficacy in other clinical indications. The main objective was to evaluate the biological variation of these glycoproteins using two different immunoassays in an apparently healthy Caucasian population. METHODS: Nineteen healthy volunteers including 11 women and 8 men were sampled weekly for 5 consecutive weeks. Samples were analyzed in duplicate on Lumipulse® G600II (Fujirebio) and on the Cobas e602 (Roche Diagnostics) analyzers. After assessment of normality, exclusion of outliers and analysis of homogeneity of variance, analytical variation (CVA), within-subject biological variation (CVI) and between-subject biological variation (CVG) were determined using a nested ANOVA. RESULTS: CVA, CVI and CVG were determined on both analyzers and both genders. For CA 125, the CVA ranges from 1.0 to 3.4%, the CVI from 5.7 to 13.8% and the CVG from 32.2 to 42.9%. For CA 15-3, the CVA is between 1.1 and 3.4%, the CVI between 3.9 and 6.5% and the CVG between 43.7 and 196.9%. Lastly, HE 4 has CVA values between 1.4 and 2.4%, CVI between 5.1 and 10.5% and CVG between 7.1 and 12.6%. CONCLUSIONS: Our study provided updated data on the biological variation of CA 125, HE 4 and CA 15-3. These data allow to improve the clinical interpretation and thus the management of the patient.

Biological investigations of transfusion reactions: Contribution of symptom-based decisional algorithms.

OBJECTIVES: While transfusion is a common and safe therapeutic procedure in health care facilities, transfusion reactions can occur, whether acute or delayed, mild or life-threatening. In face of these reactions, the biological analysis laboratory plays a central role in their diagnosis. The objective of this article is to develop decisional algorithms for laboratory tests to be performed according to the clinical symptoms developed by the patient during or after transfusion. METHODS: Based on the information collected by reviewing the literature and the procedures used in our hospital, we then developed biological investigation algorithms according to the symptoms presented by the patient, rather than the presumed reaction. RESULTS AND CONCLUSION: We have developed symptom-based algorithms for acute transfusion reactions management that streamline laboratory testing and simplify the differential diagnosis.

The age of the opening of the Ice-Free Corridor and implications for the peopling of the Americas.

SignificanceThe Ice-Free Corridor (IFC) has long played a key role in hypotheses about the peopling of the Americas. Earlier assessments of its age suggested that the IFC was available for a Clovis-first migration, but subsequent developments now suggest a pre-Clovis occupation of the Americas that occurred before the opening of the IFC, thus supporting a Pacific coastal migration route instead. However, large uncertainties in existing ages from the IFC cannot preclude its availability as a route for the first migrations. Resolving this debate over migration route is important for addressing the questions of when and how the first Americans arrived. We report cosmogenic nuclide exposure ages that show that the final opening of the IFC occurred well after pre-Clovis occupation.

Challenges of biological monitoring in a hemophilia A patient without inhibitors on emicizumab undergoing major orthopedic surgery: a case report.

A man with severe hemophilia A (HA) without factor VIII (FVIII) inhibitors was admitted for total arthroplasty of his elbow. The patient was being treated with emicizumab, with his last administration given 8 days before surgery. Preoperatively, he received a bolus of 4000 international units (IU) of recombinant (r)FVIII. Throughout the operation, a continuous infusion of 4 IU/kg/h was administered and maintained over 24 hours. On the first postoperative day, the FVIII infusion rate was reduced to 225 IU/h for 4 days and stopped on the fifth day. Under this treatment, no bleeding complications occurred. Emicizumab is known to interfere with a wide range of coagulation assays, thereby challenging replacement therapy monitoring before, during, and after surgery. In this case study, we report on the assessment of FVIII levels at different time points using various reagents. We conclude that for both hematologists and non-hematology clinicians, it is crucial to be aware of emicizumab interferences with routine coagulation tests so as to avoid misinterpretation. In addition, laboratory specialists must be familiar with this treatment in order to select appropriate coagulation tests and provide rapid and reliable result interpretations.

Assessing the health benefits of advice services: using research evidence and logic model methods to explore complex pathways.

Poverty is positively associated with poor health; thus, some healthcare commissioners in the UK have pioneered the introduction of advice services in health service locations. Previous systematic reviews have found little direct evidence for a causal relationship between the provision of advice and physical health and limited evidence for mental health improvement. This paper reports a study using a broader range of types of research evidence to construct a conceptual (logic) model of the wider evidence underpinning potential (rather than only proven) causal pathways between the provision of advice services and improvements in health. Data and discussion from 87 documents were used to construct a model describing interventions, primary outcomes, secondary and tertiary outcomes following advice interventions. The model portrays complex causal pathways between the intervention and various health outcomes; it also indicates the level of evidence for each pathway. It can be used to inform the development of research designed to evaluate the pathways between interventions and health outcomes, which will determine the impact on health outcomes and may explain inconsistencies in previous research findings. It may also be useful to commissioners and practitioners in making decisions regarding development and commissioning of advice services.

Systematic review and narrative synthesis of the effectiveness of contraceptive service interventions for young people, delivered in health care settings.

A systematic review and narrative synthesis to determine the effectiveness of contraception service interventions for young people delivered in health care premises was undertaken. We searched 12 key health and medical databases, reference lists of included papers and systematic reviews and cited reference searches on included articles. All retrieved literature was screened at title and abstract levels, and relevant articles were taken through to full paper appraisal. Data relating to study design, outcomes and quality were extracted by one reviewer and independently checked by a second reviewer. We included interventions that consisted of contraceptive service provision for young people, and also interventions to encourage young people to use existing contraceptive services. The searches identified 23 studies that met the inclusion criteria. The papers focused on: new adolescent services, outreach to existing services, advanced provision of emergency contraception, condom/contraceptive provision and advice and repeat pregnancy prevention. The literature in general is not well developed in terms of good quality effectiveness studies and key outcome measures. However, it is possible to make recommendations in terms of outreach versus targeted young people's services in health care settings, advanced provision of emergency contraception and long-acting reversible contraception to prevent repeat adolescent pregnancy.

Factors influencing advanced practice nurses' ability to promote evidence-based practice among frontline nurses.

BACKGROUND: Advanced practice nurses (APNs) have an important role in promoting evidence-based practice (EBP) among frontline nurses (FLNs). Factors influencing FLNs' engagement with EBP are well documented but little is known about factors that affect APNs' ability to facilitate evidence in practice. AIMS: To identify factors that influence APNs' ability to promote EBP among FLNs. METHODS: A multiple case study of 23 APNs from hospital and primary care settings across seven English health authorities was undertaken. Data collection comprised interviews and observation of APNs and interviews with FLNs and other healthcare professionals. Data were analysed using the Framework approach. FINDINGS: Four groups of influencing factors were identified: (1) Personal attributes of APNs included knowledge and skills in EBP, clinical credibility with frontline staff and leadership style. (2) Relationships with stakeholders included APNs' interactions with FLNs and the level of support from managers and medical colleagues. (3) Aspects of the APN role included their sphere of responsibility and workload. (4) Organisational context included the organisational culture, FLNs' workload, professional networks and available resources. IMPLICATIONS: Educational preparation for APNs should enable them to develop expertise in EBP plus interpersonal and leadership skills to manage relational dynamics in clinical settings. APN role specifications should provide the opportunity to promote EBP. The organisational culture should be conducive to enabling EBP with managers supportive of this aspect of the APNs' role. CONCLUSIONS: APNs need to be supported to address the individual, interpersonal and organisational factors, which influence their ability to promote EBP. Organisational commitment at the highest level is key to APNs' ability to fulfil this aspect of their role.

Further challenges to medical dominance? The case of nurse and pharmacist supplementary prescribing.

Doctors have traditionally been viewed as the dominant healthcare profession, with the authority to prescribe medicines, but recent non-medical prescribing initiatives have been viewed as possible challenges to such dominance. Using the example of the introduction of supplementary prescribing in the UK, this study sought to explore whether such initiatives represent a challenge to medical authority. Ten case study sites in England involving primary and secondary care and a range of clinical areas were used to undertake a total of 77 observations of supplementary prescribing consultations and interviews with 28 patients, 11 doctors and nurse and pharmacist prescribers at each site. Supplementary prescribing was viewed positively by all participants but several doctors and patients appeared to lack awareness and understanding of supplementary prescribing. Continued medical authority was supported empirically in five areas: patients' and supplementary prescribers' perception of doctors as being hierarchically superior; doctors legitimation of nurses' and pharmacists' prescribing initially; doctors' belief that they could control (particularly nurses') access to prescribing training; supplementary prescribers' frequent recourse to use doctors' advice, coupled with doctors' encouragement of such 'knock on door' prescribing advice policies; doctors' denigration of most routine prescribing but claims that diagnosis was more skilled and key to medicine. Supplementary prescribing appeared to be successfully accomplished in practice in a range of clinical settings and was acceptable to all involved but did not ultimately challenge medical dominance. However, more recent nurse and pharmacist independent prescribing (involving diagnosis) may represent a more significant threat.

Behavioural interventions for weight management in pregnancy: a systematic review of quantitative and qualitative data.

BACKGROUND: There is a rising prevalence of excessive weight gain in pregnancy and an increasing number of pregnant women who are overweight or obese at the start of the pregnancy. Excessive weight gain during pregnancy is associated with adverse maternal and neonatal consequences and increases the risk of long-term obesity. Pregnancy therefore may be a key time to prevent excessive weight gain and improve the health of women and their unborn child. This systematic review sought to assess the effectiveness of behavioural interventions to prevent excessive weight gain in pregnancy and explore the factors that influence intervention effectiveness. METHODS: We undertook a systematic review of quantitative and qualitative evidence. This included a meta-analysis of controlled trials of diet and physical activity interventions to prevent excessive weight gain during pregnancy and a thematic synthesis of qualitative studies that investigated the views of women on weight management during pregnancy. A thorough search of eleven electronic bibliographic databases, reference lists of included studies, relevant review articles and experts in the field were contacted to identify potentially relevant studies.Two independent reviewers extracted data. RevMan software was used to perform the meta-analyses. Qualitative data was subject to thematic analysis. Both quantitative and qualitative data were aligned using a matrix framework. RESULTS: Five controlled trials and eight qualitative studies were included. The overall pooled effect size found no significant difference in gestational weight gain amongst participants in the intervention group compared with the control group (mean difference -0.28 95% CI -0.64 to 0.09). The study designs, participants and interventions all varied markedly and there was significant heterogeneity within this comparison in the meta-analysis (I2 67%). Subgroup and sensitivity analysis did not identify contextual elements that influenced the effectiveness of the intervention.In a thematic analysis of the qualitative studies, three major themes emerged relating to women's views of weight management in pregnancy: pregnancy as a time of transition and change, conflicting and contradictory messages and a perceived lack of control. When the results of both quantitative and qualitative data were aligned it was clear that some of the barriers that women described in achieving healthy weight gain in pregnancy were not addressed by the interventions evaluated. This may have contributed to the limited effectiveness of the interventions. CONCLUSIONS: Despite intense and often tailored interventions there was no statistically significant effect on weight gain during pregnancy. Inadequate and often contradictory information regarding healthy weight management was reported by women in qualitative studies and this was addressed in the interventions but this in itself was insufficient to lead to reduced weight gain. Multiple types of interventions, including community based strategies are needed to address this complex health problem.

The role of advanced practice nurses in knowledge brokering as a means of promoting evidence-based practice among clinical nurses.

AIM: To identify approaches used by advanced practice nurses to promote evidence-based practice among clinical nurses. BACKGROUND: Barriers encountered at individual and organizational levels hinder clinical nurses in their ability to deliver evidence-based practice. Advanced practice nurses are well placed to promote evidence-based practice through interactions with clinical nurses. However, little is understood about how advanced practice nurses might realize this potential. METHOD: A multiple instrumental case study of 23 advanced practice nurses from hospital and primary care settings across seven Strategic Health Authorities in England was undertaken in 2006. Data collection comprised interviews and observation of advanced practice nurses and interviews with clinical nurses and other healthcare professionals. Data were analysed using the Framework approach. FINDINGS: Advanced practice nurses acted as knowledge brokers in promoting evidence-based practice among clinical nurses. Knowledge management and promoting the uptake of knowledge were key components of knowledge brokering. Knowledge management involved generating different types of evidence, accumulating evidence to act as a repository for clinical nurses, synthesizing different forms of evidence, translating evidence by evaluating, interpreting and distilling it for different audiences and disseminating evidence by formal and informal means. Advanced practice nurses promoted the uptake of evidence by developing the knowledge and skills of clinical nurses through role modelling, teaching, clinical problem-solving and facilitating change. CONCLUSION: The role of advanced practice nurses in knowledge brokering is complex and multi-faceted. It extends beyond the knowledge management, linkage and capacity building identified in the literature to include active processes of problem-solving and facilitating change.

Views of contraceptive service delivery to young people in the UK: a systematic review and thematic synthesis.

BACKGROUND AND METHODOLOGY: Despite widespread availability of contraceptives and increasing service provision in the UK, rates of teenage pregnancy remain a concern. It has been suggested that young people face particular obstacles in accessing services, leading to a need for specialist provision. This systematic review examined the literature reporting views of service providers and young people. Data were synthesised in order to develop key themes to inform the development of contraceptive services for this population. RESULTS: A total of 59 papers reporting studies carried out within the UK were included. Forty-five of these provided qualitative or mixed method data and 14 reported survey findings. Seven key themes were identified: perceptions of services; accessibility; embarrassment; anonymity and confidentiality; the clinic environment; the consultation; and service organisation. CONCLUSIONS: This review suggests that the most significant concern for young people is the preservation of anonymity and confidentiality. There seems to be a need for young people to be given greater assurances about this, with process and environmental changes suggested. The fear of staff being critical or unfriendly also presents a considerable obstacle to some young people. Issues of service accessibility - such as convenience of location and opening hours - are also highlighted, with lifestyle factors and restrictions on where under-18s can go suggested as important aspects. The review suggests that varying preferences among young people with regard to which service to access requires choice to be preserved and, where possible, extended. This requires services to work effectively together to consider provision across a locality.

Views regarding the use of contraception amongst young people in the UK: a systematic review and thematic synthesis.

OBJECTIVES: The high rate of teenage pregnancy in the United Kingdom continues to be a concern. Factors such as living in a deprived area, poor educational attainment, and living in state-provided care homes have been associated with a greater risk of young motherhood. This study aimed to examine the literature describing perceptions of young people, with a view to gaining a greater understanding of individual contraceptive use and risk factors for young motherhood. METHODS: A systematic review of studies reporting qualitative data was undertaken. Data were synthesised to develop key themes. RESULTS: Thirty-four papers using qualitative or mixed methods were included in the review. Five key themes are reported; they relate to: use or non-use of contraceptives; attitude to pregnancy; views regarding different forms of contraception; influences on views; gender differences. CONCLUSIONS: The review highlights that individual conceptions of risk, differing perceptions of benefits and concerns regarding the forms of contraception, and varying attitudes towards pregnancy, continue to present obstacles to changing behaviour, particularly in high risk groups. There seems to be a need for interventions to further address negative perceptions of contraceptives, and place a greater emphasis on exploring value judgements regarding contraception and young motherhood.

The effectiveness of interventions to establish smoke-free homes in pregnancy and in the neonatal period: a systematic review.

This review considers the effectiveness of interventions to encourage the establishment of smoke-free homes during pregnancy and the neonatal period. A comprehensive search of the literature was undertaken to find relevant studies via electronic databases, citations and reference lists of included studies. The searches identified 17 papers that met the inclusion criteria. These were quality assessed and data extracted. Due to heterogeneity of the papers, a narrative synthesis was completed. Interventions were categorized in terms of those based on counselling, counselling plus additional elements, individually adapted programmes and motivational interviewing. The findings suggest inconclusive evidence relating to these intervention types, with a range of outcome measures reported. There were limitations throughout the papers in terms of study quality (especially sample size) and poor reporting of results in relation to effectiveness. The review was limited by its very specific population; however, it suggests that currently there is mixed evidence for the effectiveness of interventions to reduce parental environmental tobacco smoke in early infancy.

Factors influencing the contribution of advanced practice nurses to promoting evidence-based practice among front-line nurses: findings from a cross-sectional survey.

AIM: This paper is a report of a study to identify factors influencing advanced practice nurses' contribution to promoting evidence-based practice among front-line nurses. BACKGROUND: Despite widespread recognition that care should be evidence-based, nurses experience challenges implementing evidence-based practice. As opinion leaders, advanced practice nurses can influence the practice of front-line nurses by promoting research use. Little is known about how advanced practice nurses use evidence and their influence on care given by front-line nurses. METHOD: A cross-sectional survey of 855 advanced practice nurses working in 87 hospital/primary care settings in England. The questionnaire examined understandings of evidence-based practice, sources of evidence used, ways of working with front-line nurses, perceived impact on front-line nurses, skills in evidence-based practice and barriers to promoting evidence-based practice. Data were collected in 2005 and analysed using descriptive statistics. Comparisons were made between advanced practice nurses with Masters qualifications and those with lower qualifications. FINDINGS: Advanced practice nurses used different sources of evidence. They engaged in various activities to promote evidence-based practice and had a positive influence on front-line nurses' practice. Advanced practice nurses' skills in evidence-based practice varied with few considering themselves expert. Advanced practice nurses with Masters qualifications perceived themselves to be more skilled in all aspects of evidence-based practice than those with lower qualifications. CONCLUSION: Advanced practice nurses are well placed as clinical leaders to promote evidence-based practice by frontline nurses but require further development of their skills in evidence-based practice. In order to maximize their potential, advanced practice nurses require Master's preparation.

Systematic review and narrative synthesis of the effectiveness of contraceptive service interventions for young people, delivered in educational settings.

STUDY OBJECTIVE: This review was undertaken to determine the effectiveness of contraception service interventions for young people that were delivered in educational settings. DESIGN: We conducted a systematic review and narrative synthesis. SETTING: Interventions were included where they were delivered in educational institutions, including schools, colleges, and pupil referral units. PARTICIPANTS: Young people aged 19 and under. Studies of wider age groups were included if the majority of participants were aged under 19 years. INTERVENTIONS: We included interventions which consisted of contraceptive service provision, and also interventions to encourage young people to use existing contraceptive services. MAIN OUTCOME MEASURES: The main outcome measures used in the studies were: rate of teenage pregnancy, rate of contraceptive use, and sexual behavior. Many outcome measures were self reported. RESULTS: Twenty-nine papers were included which reported on interventions to prevent adolescent pregnancy (and repeat pregnancy), school-based health centers, contraceptive use in college students, and multicomponent interventions. Intensive case management intervention conducted by a culturally matched school-based social worker (along with other components including peer education) were shown to be effective in preventing repeat adolescent pregnancy, at least for the duration of the intervention. Also, school-based health centers appear to be most effective when contraception provision is made available on site. CONCLUSIONS: The evidence from these papers is limited, in terms of both quality and quantity, along with consistency of findings, but some recommendations in relation to effective interventions can be made.

Factors relating to the uptake of interventions for smoking cessation among pregnant women: a systematic review and qualitative synthesis.

INTRODUCTION: The review had the aim of investigating factors enabling or discouraging the uptake of smoking cessation services by pregnant women smokers. METHODS: The literature was searched for papers relating to the delivery of services to pregnant or recently pregnant women who smoke. No restrictions were placed on study design. A qualitative synthesis strategy was adopted to analyze the included papers. RESULTS: Analysis and synthesis of the 23 included papers suggested 10 aspects of service delivery that may have an influence on the uptake of interventions. These were whether or not the subject of smoking is broached by a health professional, the content of advice and information provided, the manner of communication, having service protocols, follow-up discussion, staff confidence in their skills, the impact of time and resource constraints, staff perceptions of ineffectiveness, differences between professionals, and obstacles to accessing interventions. DISCUSSION: The findings suggest variation in practice between services and different professional groups, in particular regarding the recommendation of quitting smoking versus cutting down but also in regard to procedural aspects, such as recording status and repeat advice giving. These differences offer the potential for a pregnant woman to receive contradicting advice. The review suggests a need for greater training in this area and the greater use of protocols, with evidence of a perception of ineffectiveness/pessimism toward intervention among some service providers.

Learning to prescribe - pharmacists' experiences of supplementary prescribing training in England.

BACKGROUND: The introduction of non-medical prescribing for professions such as pharmacy and nursing in recent years offers additional responsibilities and opportunities but attendant training issues. In the UK and in contrast to some international models, becoming a non-medical prescriber involves the completion of an accredited training course offered by many higher education institutions, where the skills and knowledge necessary for prescribing are learnt. AIMS: to explore pharmacists' perceptions and experiences of learning to prescribe on supplementary prescribing (SP) courses, particularly in relation to inter-professional learning, course content and subsequent use of prescribing in practice. METHODS: A postal questionnaire survey was sent to all 808 SP registered pharmacists in England in April 2007, exploring demographic, training, prescribing, safety culture and general perceptions of SP. RESULTS: After one follow-up, 411 (51%) of pharmacists responded. 82% agreed SP training was useful, 58% agreed courses provided appropriate knowledge and 62% agreed that the necessary prescribing skills were gained. Clinical examination, consultation skills training and practical experience with doctors were valued highly; pharmacology training and some aspects of course delivery were criticised. Mixed views on inter-professional learning were reported - insights into other professions being valued but knowledge and skills differences considered problematic. 67% believed SP and recent independent prescribing (IP) should be taught together, with more diagnostic training wanted; few pharmacists trained in IP, but many were training or intending to train. There was no association between pharmacists' attitudes towards prescribing training and when they undertook training between 2004 and 2007 but earlier cohorts were more likely to be using supplementary prescribing in practice. CONCLUSION: Pharmacists appeared to value their SP training and suggested improvements that could inform future courses. The benefits of inter-professional learning, however, may conflict with providing profession-specific training. SP training may be perceived to be an instrumental 'stepping stone' in pharmacists' professional project of gaining full IP status.