Negative interference from immunoglobulin M paraproteinaemia on the Roche enzymatic creatinine method.

Although enzymatic creatinine methods are subject to fewer interferences than traditional Jaffe creatinine methods, every method in clinical chemistry has limitations. We report, for the first time in the literature, a case of an immunoglobulin M (IgM) paraproteinaemia causing an undetectably low creatinine result on the Roche enzymatic assay. This interference did not occur with other enzymatic creatinine methods produced by Abbott and Siemens or the Roche Jaffe, VITROS dry slide and liquid chromatography with tandem mass spectrometry (LC-MS/MS) creatinine methods. IgM interference was confirmed as patient serum precipitated with polyethylene glycol (PEG) and anti-IgM antiserum yielded detectable Roche enzymatic creatinine results comparable to unaffected methods. The patient's serum formed an obvious precipitate when mixed with reagent one of the Roche enzymatic creatinine method. This is in contrast to a report of positive interference from IgM paraproteinaemia in a different enzymatic creatinine method, which showed that a precipitate formed when mixing blood with reagent two. As each patient's paraprotein has a unique structure, it is possible that there are variations in the chemical characteristics of IgM paraproteins between patients. This, as well as IgM-class antibodies' tendency to form multimers and aggregates, can lead to unpredictable assay interferences and precipitation tendencies between different manufacturers of enzymatic creatinine reagents and their incubation steps. This case highlights the importance of continuing to question and investigates results that do not fit the clinical picture, especially as more laboratories switch from primarily using traditional Jaffe creatinine methods to enzymatic creatinine methods.

Case report: Interference from isatuximab on serum protein electrophoresis prevented demonstration of complete remission in a myeloma patient.

Multiple myeloma is a haematological cancer caused by malignant plasma cells in the bone marrow that can result in organ dysfunction and death. Recent novel treatments have contributed to improved survival rates, including monoclonal antibody therapies that target the CD38 protein on the surface of plasma cells. Anti-CD38 therapies are IgG kappa monoclonal antibodies that are given in doses high enough for the drug to be visible on serum protein electrophoresis as a small paraprotein. We present a case where isatuximab, the most recent anti-CD38 monoclonal antibody to be approved for treatment of myeloma, obscured the patient's paraprotein on gel immunofixation, so that complete remission could not be demonstrated. This was resolved using the isatuximab Hydrashift assay. The interference on gel immunofixation was unexpected because isatuximab migrated in a position distinct from the patient's paraprotein on capillary zone electrophoresis. We demonstrate the surprising finding that isatuximab migrates in a different position on gel electrophoresis compared to capillary zone electrophoresis. It is vital that laboratories are aware of the possible interference on electrophoresis from anti-CD38 monoclonal antibody therapies, and are able to recognise these drugs on protein electrophoresis. The difference in isatuximab's electrophoretic mobility on capillary and gel protein electrophoresis makes this particularly challenging. Laboratories should have a strategy for alternative analyses in the event that the drugs interfere with assessment of the patient's paraprotein.

Achieving Spread, Scale Up and Sustainability of Video Consulting Services During the COVID-19 Pandemic? Findings From a Comparative Case Study of Policy Implementation in England, Wales, Scotland and Northern Ireland.

Requirements for physical distancing as a result of COVID-19 and the need to reduce the risk of infection prompted policy supporting rapid roll out of video consulting across the four nations of the UK-England, Northern Ireland, Scotland and Wales. Drawing on three studies of the accelerated implementation and uptake of video consulting across the four nations, we present a comparative and interpretive policy analysis of the spread and scale-up of video consulting during the pandemic. Data include interviews with 59 national level stakeholders, 55 health and social care staff and 30 patients, 20 national documents, responses to a UK-wide survey of NHS staff and analysis of routine activity data. Sampling ensured variations in geography, clinical context and adoption progress across the combined dataset. Comparative analysis was guided by theory on policy implementation and crisis management. The pandemic provided a "burning platform" prompting UK-wide policy supporting the use of video consulting in health care as a critical means of managing the risk of infection and a standard mode of provision. This policy push facilitated interest in video consulting across the UK. There was, however, marked variation in how this was put into practice across the four nations. Pre-existing infrastructure, policies and incentives for video consulting in Scotland, combined with a collaborative system-level approach, a program dedicated to developing video-based services and resourcing and supporting staff to deliver them enabled widespread buy-in and rapid spread. In England, Wales and Northern Ireland, pre-existing support for digital health (e.g., hardware, incentives) and virtual care, combined with reduced regulation and "light touch" procurement managed to override some (but by no means all) cultural barriers and professional resistance to implementing digital change. In Northern Ireland and Wales, limited infrastructure muted spread. In all three countries, significant effort at system level to develop, review and run video consulting programs enabled a substantial number of providers to change their practice, albeit variably across settings. Across all four nations ongoing uncertainty, potential restructuring and tightening of regulations, along with difficulties inherent in addressing inequalities in digital access, raise questions about the longer-term sustainability of changes to-date.

Video Consultations Between Patients and Clinicians in Diabetes, Cancer, and Heart Failure Services: Linguistic Ethnographic Study of Video-Mediated Interaction.

BACKGROUND: Video-mediated clinical consultations offer potential benefits over conventional face-to-face in terms of access, convenience, and sometimes cost. The improved technical quality and dependability of video-mediated consultations has opened up the possibility for more widespread use. However, questions remain regarding clinical quality and safety. Video-mediated consultations are sometimes criticized for being not as good as face-to-face, but there has been little previous in-depth research on their interactional dynamics, and no agreement on what a good video consultation looks like. OBJECTIVE: Using conversation analysis, this study aimed to identify and analyze the communication strategies through which video-mediated consultations are accomplished and to produce recommendations for patients and clinicians to improve the communicative quality of such consultations. METHODS: We conducted an in-depth analysis of the clinician-patient interaction in a sample of video-mediated consultations and a comparison sample of face-to-face consultations drawn from 4 clinical settings across 2 trusts (1 community and 1 acute care) in the UK National Health Service. The video dataset consisted of 37 recordings of video-mediated consultations (with diabetes, antenatal diabetes, cancer, and heart failure patients), 28 matched audio recordings of face-to-face consultations, and fieldnotes from before and after each consultation. We also conducted 37 interviews with staff and 26 interviews with patients. Using linguistic ethnography (combining analysis of communication with an appreciation of the context in which it takes place), we examined in detail how video interaction was mediated by 2 software platforms (Skype and FaceTime). RESULTS: Patients had been selected by their clinician as appropriate for video-mediated consultation. Most consultations in our sample were technically and clinically unproblematic. However, we identified 3 interactional challenges: (1) opening the video consultation, (2) dealing with disruption to conversational flow (eg, technical issues with audio and/or video), and (3) conducting an examination. Operational and technological issues were the exception rather than the norm. In all but 1 case, both clinicians and patients (deliberately or intuitively) used established communication strategies to successfully negotiate these challenges. Remote physical examinations required the patient (and, in some cases, a relative) to simultaneously follow instructions and manipulate technology (eg, camera) to make it possible for the clinician to see and hear adequately. CONCLUSIONS: A remote video link alters how patients and clinicians interact and may adversely affect the flow of conversation. However, our data suggest that when such problems occur, clinicians and patients can work collaboratively to find ways to overcome them. There is potential for a limited physical examination to be undertaken remotely with some patients and in some conditions, but this appears to need complex interactional work by the patient and/or their relatives. We offer preliminary guidance for patients and clinicians on what is and is not feasible when consulting via a video link. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/10913.

Technology-Enhanced Consultations in Diabetes, Cancer, and Heart Failure: Protocol for the Qualitative Analysis of Remote Consultations (QuARC) Project.

BACKGROUND: Remote videoconsulting is promoted by policy makers as a way of delivering health care efficiently to an aging population with rising rates of chronic illness. As a radically new service model, it brings operational and interactional challenges in using digital technologies. In-depth research on this dynamic is needed before remote consultations are introduced more widely. OBJECTIVE: The objective of this study will be to identify and analyze the communication strategies through which remote consultations are accomplished and to guide patients and clinicians to improve the communicative quality of remote consultations. METHODS: In previous research, we collected and analyzed two separate datasets of remote consultations in a National Institute for Health Research-funded study of clinics in East London using Skype and a Wellcome Trust-funded study of specialist community heart failure teams in Oxford using Skype or FaceTime. The Qualitative Analysis of Remote Consultations (QuARC) study will combine datasets and undertake detailed interactional microanalysis of up to 40 remote consultations undertaken by senior and junior doctors and nurse specialists, including consultations with adults with diabetes, women who have diabetes during pregnancy, people consulting for postoperative cancer surgery and community-based patients having routine heart failure reviews along with up to 25 comparable face-to-face consultations. Drawing on established techniques (eg, conversation analysis), analysis will examine the contextual features in remote consultations (eg, restricted visual field) combined with close analysis of different modes of communication (eg, speech, gesture, and gaze). RESULTS: Our findings will address the current gap in knowledge about how technology shapes the fine detail of communication in remote consultations. Alongside academic outputs, findings will inform the coproduction of information and guidance about communication strategies to support successful remote consultations. CONCLUSIONS: Identifying the communication strategies through which remote consultations are accomplished and producing guidance for patients and clinicians about how to use this kind of technology successfully in consultations is an important and timely goal because roll out of remote consultations is planned across the National Health Service. REGISTERED REPORT IDENTIFIER: RR1-10.2196/10913.

Real-World Implementation of Video Outpatient Consultations at Macro, Meso, and Micro Levels: Mixed-Method Study.

BACKGROUND: There is much interest in virtual consultations using video technology. Randomized controlled trials have shown video consultations to be acceptable, safe, and effective in selected conditions and circumstances. However, this model has rarely been mainstreamed and sustained in real-world settings. OBJECTIVE: The study sought to (1) define good practice and inform implementation of video outpatient consultations and (2) generate transferable knowledge about challenges to scaling up and routinizing this service model. METHODS: A multilevel, mixed-method study of Skype video consultations (micro level) was embedded in an organizational case study (meso level), taking account of national context and wider influences (macro level). The study followed the introduction of video outpatient consultations in three clinical services (diabetes, diabetes antenatal, and cancer surgery) in a National Health Service trust (covering three hospitals) in London, United Kingdom. Data sources included 36 national-level stakeholders (exploratory and semistructured interviews), longitudinal organizational ethnography (300 hours of observations; 24 staff interviews), 30 videotaped remote consultations, 17 audiotaped face-to-face consultations, and national and local documents. Qualitative data, analyzed using sociotechnical change theories, addressed staff and patient experience and organizational and system drivers. Quantitative data, analyzed via descriptive statistics, included uptake of video consultations by staff and patients and microcategorization of different kinds of talk (using the Roter interaction analysis system). RESULTS: When clinical, technical, and practical preconditions were met, video consultations appeared safe and were popular with some patients and staff. Compared with face-to-face consultations for similar conditions, video consultations were very slightly shorter, patients did slightly more talking, and both parties sometimes needed to make explicit things that typically remained implicit in a traditional encounter. Video consultations appeared to work better when the clinician and patient already knew and trusted each other. Some clinicians used Skype adaptively to respond to patient requests for ad hoc encounters in a way that appeared to strengthen supported self-management. The reality of establishing video outpatient services in a busy and financially stretched acute hospital setting proved more complex and time-consuming than originally anticipated. By the end of this study, between 2% and 22% of consultations were being undertaken remotely by participating clinicians. In the remainder, clinicians chose not to participate, or video consultations were considered impractical, technically unachievable, or clinically inadvisable. Technical challenges were typically minor but potentially prohibitive. CONCLUSIONS: Video outpatient consultations appear safe, effective, and convenient for patients in situations where participating clinicians judge them clinically appropriate, but such situations are a fraction of the overall clinic workload. As with other technological innovations, some clinicians will adopt readily, whereas others will need incentives and support. There are complex challenges to embedding video consultation services within routine practice in organizations that are hesitant to change, especially in times of austerity.

What is the current evidence of the impact on quality of life whilst waiting for management/treatment of orthopaedic/musculoskeletal complaints? A systematic scoping review.

PURPOSE: To describe quality of life (QoL) outcome measures that are reported in the literature in patients waiting for outpatient orthopaedic/musculoskeletal specialist care and how waiting impacts on QoL in these terms. METHODS: A subset of studies reporting on QoL outcome measures were extracted from literature identified in a recent scoping search of Medline, Embase, Pubmed, NHS Economic Evaluation Database (Prospero registration CRD42016047332). The systematic scoping search examined impacts on patients waiting for orthopaedic specialist care. Two independent reviewers ranked study design using the National Health and Medical Research Council aetiology evidence hierarchy, and appraised study quality using Critical Appraisal Skills Programme tools. QoL measures were mapped against waiting period timepoints. RESULTS: The scoping search yielded 142 articles, of which 18 reported on impact on QoL. These studies reported only on patients waiting for hip and/or knee replacement surgery. The most recent study reported on data collected in 2006/7. The Western Ontario and McMaster Universities Arthritis Index and the SF-36 were the most commonly reported QoL measures. QoL was measured at variable timepoints in the waiting period (from a few weeks to greater than 12 months). The impact of waiting on QoL was inconsistent. CONCLUSION: The evidence base was over 10 years old, reported only on patients with hip and knee problems, and on limited QoL outcome measures, and with inconsistent findings. A better understanding of the impact on QoL for patients waiting for specialist care could be gained by using standard timepoints in the waiting period, patients with other orthopaedic conditions, comprehensive QoL measures, as well as expectations, choices and perspectives of patients waiting for specialist care.

Evaluation of community-level interventions to increase early initiation of antenatal care in pregnancy: protocol for the Community REACH study, a cluster randomised controlled trial with integrated process and economic evaluations.

BACKGROUND: The provision of high-quality maternity services is a priority for reducing inequalities in health outcomes for mothers and infants. Best practice includes women having their initial antenatal appointment within the first trimester of pregnancy in order to provide screening and support for healthy lifestyles, well-being and self-care in pregnancy. Previous research has identified inequalities in access to antenatal care, yet there is little evidence on interventions to improve early initiation of antenatal care. The Community REACH trial will assess the effectiveness and cost-effectiveness of engaging communities in the co-production and delivery of an intervention that addresses this issue. METHODS/DESIGN: The study design is a matched cluster randomised controlled trial with integrated process and economic evaluations. The unit of randomisation is electoral ward. The intervention will be delivered in 10 wards; 10 comparator wards will have normal practice. The primary outcome is the proportion of pregnant women attending their antenatal booking appointment by the 12th completed week of pregnancy. This and a number of secondary outcomes will be assessed for cohorts of women (n = approximately 1450 per arm) who give birth 2-7 and 8-13 months after intervention delivery completion in the included wards, using routinely collected maternity data. Eight hospitals commissioned to provide maternity services in six NHS trusts in north and east London and Essex have been recruited to the study. These trusts will provide anonymised routine data for randomisation and outcomes analysis. The process evaluation will examine intervention implementation, acceptability, reach and possible causal pathways. The economic evaluation will use a cost-consequences analysis and decision model to evaluate the intervention. Targeted community engagement in the research process was a priority. DISCUSSION: Community REACH aims to increase early initiation of antenatal care using an intervention that is co-produced and delivered by local communities. This pragmatic cluster randomised controlled trial, with integrated process and economic evaluation, aims to rigorously assess the effectiveness of this public health intervention, which is particularly complex due to the required combination of standardisation with local flexibility. It will also answer questions about scalability and generalisability. TRIAL REGISTRATION: ISRCTN registry: registration number 63066975 . Registered on 18 August 2015.

SCA-1 Labels a Subset of Estrogen-Responsive Bipotential Repopulating Cells within the CD24+ CD49fhi Mammary Stem Cell-Enriched Compartment.

Estrogen stimulates breast development during puberty and mammary tumors in adulthood through estrogen receptor-α (ERα). These effects are proposed to occur via ERα+ luminal cells and not the mammary stem cells (MaSCs) that are ERαneg. Since ERα+ luminal cells express stem cell antigen-1 (SCA-1), we sought to determine if SCA-1 could define an ERα+ subset of EpCAM+/CD24+/CD49fhi MaSCs. We show that the MaSC population has a distinct SCA-1+ population that is abundant in pre-pubertal mammary glands. The SCA-1+ MaSCs have less stem cell markers and less in vivo repopulating activity than their SCA-1neg counterparts. However, they express ERα and specifically enter the cell cycle at puberty. Using estrogen-deficient aromatase knockouts (ArKO), we showed that the SCA-1+ MaSC could be directly modulated by estrogen supplementation. Thus, SCA-1 enriches for an ERα+, estrogen-sensitive subpopulation within the CD24+/CD49fhi MaSC population that may be responsible for the hormonal sensitivity of the developing mammary gland.

Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors.

Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world's poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5-isoxazoles, furoxans, and furazans. Several of these compounds maintain low-micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.

Timing of the initiation of antenatal care: An exploratory qualitative study of women and service providers in East London.

OBJECTIVE: to explore the factors which influence the timing of the initiation of a package of publically-funded antenatal care for pregnant women living in a diverse urban setting DESIGN: a qualitative study involving thematic analysis of 21 individual interviews and six focus group discussions. SETTING: Newham, a culturally diverse borough in East London, UK PARTICIPANTS: individual interviews were conducted with 21 pregnant and postnatal women and focus group discussions were conducted with a total of 26 health service staff members(midwives and bilingual health advocates) and 32 women from four community groups (Bangladeshi, Somali, Lithuanian and Polish). FINDINGS: initial care-seeking by pregnant women is influenced by the perception that the package of antenatal care offered by the National Health Service is for viable and continuing pregnancies, as well as little perceived urgency in initiating antenatal care. This is particularly true when set against competing responsibilities and commitments in women's lives and for pregnancies with no apparent complications or disconcerting symptoms. Barriers to access to this package of antenatal care include difficulties in navigating the health service and referral system, which are compounded for women unable to speak English, and service provider delays in the processing of referrals. Accessing antenatal care was sometimes equated with relinquishing control, particularly for young women and women for whom language barriers prohibit active engagement with care. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: if women are to be encouraged to seek antenatal care from maternity services early in pregnancy, the purpose and value to all women of doing so need to be made clear across the communities in which they live. As a woman may need time to accept her pregnancy and address other priorities in her life before seeking antenatal care, it is crucial that once she does decide to seek such care, access is quick and easy. Difficulties found in navigating the system of referral for antenatal care point to a need for improved access to primary care and a simple and efficient process of direct referral to antenatal care, alongside the delivery of antenatal care which is woman-centred and experienced as empowering.

Virtual online consultations: advantages and limitations (VOCAL) study.

INTRODUCTION: Remote video consultations between clinician and patient are technically possible and increasingly acceptable. They are being introduced in some settings alongside (and occasionally replacing) face-to-face or telephone consultations. METHODS: To explore the advantages and limitations of video consultations, we will conduct in-depth qualitative studies of real consultations (microlevel) embedded in an organisational case study (mesolevel), taking account of national context (macrolevel). The study is based in 2 contrasting clinical settings (diabetes and cancer) in a National Health Service (NHS) acute trust in London, UK. Main data sources are: microlevel--audio, video and screen capture to produce rich multimodal data on 45 remote consultations; mesolevel--interviews, ethnographic observations and analysis of documents within the trust; macrolevel--key informant interviews of national-level stakeholders and document analysis. Data will be analysed and synthesised using a sociotechnical framework developed from structuration theory. ETHICS APPROVAL: City Road and Hampstead NHS Research Ethics Committee, 9 December 2014, reference 14/LO/1883. PLANNED OUTPUTS: We plan outputs for 5 main audiences: (1) academics: research publications and conference presentations; (2) service providers: standard operating procedures, provisional operational guidance and key safety issues; (3) professional bodies and defence societies: summary of relevant findings to inform guidance to members; (4) policymakers: summary of key findings; (5) patients and carers: 'what to expect in your virtual consultation'. DISCUSSION: The research literature on video consultations is sparse. Such consultations offer potential advantages to patients (who are spared the cost and inconvenience of travel) and the healthcare system (eg, they may be more cost-effective), but fears have been expressed that they may be clinically risky and/or less acceptable to patients or staff, and they bring significant technical, logistical and regulatory challenges. We anticipate that this study will contribute to a balanced assessment of when, how and in what circumstances this model might be introduced.

What is orthopaedic triage? A systematic review.

RATIONALE, AIMS AND OBJECTIVES: Complex and chronic disease is placing significant pressure on hospital outpatient departments. Novel ways of delivering care have been developed recently and are often described as 'triage' services. This paper reviews the literature pertaining to definitions and descriptions of orthopaedic/musculoskeletal triage processes, in order to provide information on 'best practice' to assist health care facilities. METHOD: A comprehensive open-ended search was conducted using electronic databases to identify studies describing models of triage clinics for patients with a musculoskeletal/orthopaedic complaint, who have been referred to hospital outpatient clinics for a surgical consultation. Studies were critically appraised using the McMaster quality appraisal tool and ranked using the National Health and Medical Research Council hierarchy of evidence. A thematic analysis of the definitions, processes and procedures of triage described within the literature was undertaken. RESULTS: 1930 studies were identified and 45 were included in the review (including diagnostic and evaluative research). The hierarchy of evidence ranged from I to IV; however, the majority were at low levels of evidence and scored poorly on the critical appraisal tool. Three broad themes of triage were identified: presence of a referral, configuration of the triage (who, how and where) and the aim of triage. However, there were significant inconsistencies across these themes. CONCLUSIONS: This systematic review highlighted the need for standardization of the definition of triage, the procedures of assessment and management and measures of outcome used in orthopaedic/musculoskeletal triage to ensure best-practice processes, procedures and outcomes for triage clinics.

Non-natural acetogenin analogues as potent Trypanosoma brucei inhibitors.

Neglected tropical diseases remain a serious global health concern. Here, a series of novel bis-tetrahydropyran 1,4-triazole analogues based on the framework of chamuvarinin, a polyketide natural product isolated from the annonaceae plant species are detailed. The analogues synthesized display low micromolar trypanocidal activities towards both bloodstream and insect forms of Trypanosoma brucei, the causative agent of African sleeping sickness, also known as Human African Trypanosomiasis (HAT). A divergent synthetic strategy was adopted for the synthesis of the key tetrahydropyran intermediates to enable rapid access to diastereochemical variation either side of the 1,4-triazole core. The resulting diastereomeric analogues displayed varying degrees of trypanocidal activity and selectivity in structure-activity relationship studies. Together, the biological potency and calculated lipophilicity values indicate that while there is room for improvement, these derivatives may represent a promising novel class of anti-HAT agents.

Principles to guide sustainable implementation of extended-scope-of-practice physiotherapy workforce redesign initiatives in Australia: stakeholder perspectives, barriers, supports, and incentives.

Sustainable implementation of new workforce redesign initiatives requires strategies that minimize barriers and optimize supports. Such strategies could be provided by a set of guiding principles. A broad understanding of the concerns of all the key stakeholder groups is required before effective strategies and initiatives are developed. Many new workforce redesign initiatives are not underpinned by prior planning, and this threatens their uptake and sustainability. This study reports on a cross-sectional qualitative study that sought the perspectives of representatives of key stakeholders in a new workforce redesign initiative (extended-scope-of-practice physiotherapy) in one Australian tertiary hospital. The key stakeholder groups were those that had been involved in some way in the development, management, training, funding, and/or delivery of the initiative. Data were collected using semistructured questions, answered individually by interview or in writing. Responses were themed collaboratively, using descriptive analysis. Key identified themes comprised: the importance of service marketing; proactively addressing barriers; using readily understood nomenclature; demonstrating service quality and safety, monitoring adverse events, measuring health and cost outcomes; legislative issues; registration; promoting viable career pathways; developing, accrediting, and delivering a curriculum supporting physiotherapists to work outside of the usual scope; and progression from "a good idea" to established service. Health care facilities planning to implement new workforce initiatives that extend scope of usual practice should consider these issues before instigating workforce/model of care changes.

Non-medical prescribing by physiotherapists: issues reported in the current evidence.

Physiotherapists should be proactive in preparing themselves to participate in innovative models of health care, which are emerging from the healthcare workforce reforms in Australia. One challenging outcome of workforce change is physiotherapy (non-medical) prescribing (NMP), which is part of the extension of scope of physiotherapy practice. This paper summarises the current evidence base for Australian physiotherapists seeking to obtain prescribing rights. A targeted literature review was undertaken through EBSCO Host, Cochrane, Medline, SportsDiscus, Cinahl, Healthsource and Google.com using broad search terms to identify peer-reviewed and grey literature pertaining to NMP by physiotherapists, nationally and internationally. No critical appraisal was undertaken however literature was structured into the NHMRC hierarchy of evidence. Themes raised in the included literature were reported descriptively. There were six relevant peer-reviewed articles, of hierarchy levels III_3 and IV. There was however, comprehensive and recent grey literature to inform Australian physiotherapy NMP initiatives. Themes included the need for standard National action in relation to legislative and regulatory/registration issues, appropriate education, credentialing and supervisory requirements for physiotherapy prescribing. Many lessons can be learnt from the literature, including the importance of planned, uniform National action (rather than piecemeal state-by-state initiatives). Essential elements include appropriate training and skills-based recognition within the discipline and the broader health team, and the need to overtly demonstrate effectiveness and safety. Regularly-evaluated service-delivery models which support NMP by physiotherapists are further required, to demonstrate efficiency, timeliness, patient centredness and equity.

Predictors of the timing of initiation of antenatal care in an ethnically diverse urban cohort in the UK.

BACKGROUND: In the UK, women are recommended to engage with maternity services and establish a plan of care prior to the 12th completed week of pregnancy. The aim of this study was to identify predictors for late initiation of antenatal care within an ethnically diverse cohort in East London. METHODS: Cross-sectional analysis of routinely collected electronic patient record data from Newham University Hospital NHS Trust (NUHT). All women who attended their antenatal booking appointment within NUHT between 1st January 2008 and 24th January 2011 were included in this study. The main outcome measure was late antenatal booking, defined as attendance at the antenatal booking appointment after 12 weeks (+6 days) gestation. Data were analysed using multivariable logistic regression with robust standard errors. RESULTS: Late initiation of antenatal care was independently associated with non-British (White) ethnicity, inability to speak English, and non-UK maternal birthplace in the multivariable model. However, among those women who both spoke English and were born in the UK, the only ethnic group at increased risk of late booking were women who identified as African/Caribbean (aOR: 1.40: 95% CI: 1.11, 1.76) relative to British (White). Other predictors identified include maternal age younger than 20 years (aOR: 1.32; 95% CI: 1.13-1.54), high parity (aOR: 2.09; 95% CI: 1.77-2.46) and living in temporary accommodation (aOR: 1.71; 95% CI: 1.35-2.16). CONCLUSIONS: Socio-cultural factors in addition to poor English ability or assimilation may play an important role in determining early initiation of antenatal care. Future research should focus on effective interventions to encourage and enable these minority groups to engage with the maternity services.

Total synthesis, stereochemical assignment, and biological activity of chamuvarinin and structural analogues.

A highly stereocontrolled synthesis of (+)-chamuvarinin has been completed in 1.5% overall yield over 20 steps. The key fragment coupling reactions were the addition of alkyne 8 to aldehyde 7 (under Felkin-Anh control), followed by the two step activation/cyclization to close the C20-C23 2,5-cis-substituted tetrahydrofuran ring and a Julia-Kocienski olefination at C8-C9 to introduce the terminal butenolide. The inherent flexibility of our coupling strategy led to a streamlined synthesis with 17 steps in the longest sequence (2.2% overall yield), in which the key bond couplings are reversed. In addition, a series of structural analogues of chamuvarinin have been prepared and screened for activity against HeLa cancer cell lines and both the bloodstream and insect forms of Trypanosoma brucei, the parasitic agent responsible for African sleeping sickness.

Performance of the Australian Developmental Screening Test in a clinical setting.

AIMS: The study aims to assess the sensitivity and specificity of the Australian Developmental Screening Test (ADST) in a clinical setting in detecting developmental concerns that warrant further assessment or treatment. METHODS: Clients referred to an inner Sydney Community Health Centre with developmental concerns were initially assessed using the ADST, followed within 12 weeks by an assessment using the Griffiths Mental Developmental Scales (GMDS) as the gold standard. RESULTS: Of the 65 eligible children, 46 (71%) had results indicating further assessment (42) or follow-up (4) was needed (using the criteria recommended in the ADST manual). However, of these only 21 (46%) had an abnormal GMDS. This gave a sensitivity of 95% but a specificity of only 52%. New threshold criteria for further assessment were developed and applied to three age groups. If children aged under 2 years are assessed using the standard ADST threshold, and children 2 years or older are assessed using the new ADST cut-off, then the tool has a sensitivity of 95%, a specificity of 82%, a positive likelihood ratio of 5.24 (95% CI 2.78, 9.88) and negative likelihood ratio of 0.06 (0.01, 0.40). CONCLUSIONS: Modified criteria for the ADST developed in this study showed good specificity and sensitivity for detection of developmental problems in this population, referred because of developmental concerns. Further testing to see if these new criteria perform well in a different population is now needed.

The role of extended scope physiotherapists in managing patients with inflammatory arthropathies: a systematic review.

OBJECTIVES: To review the literature to identify whether, and how, physiotherapists working in extended scope of practice (ESP) engage with patients with inflammatory arthropathies. Measures of effectiveness of ESP were particularly sought. METHODS: A comprehensive library database search was conducted to identify English language studies published in full text in peer-reviewed journals during the years 2002-2012. Studies were allocated into the National Health and Medical Research Council hierarchy of evidence, but were not critically appraised. Data was extracted on conditions treated, ESP roles and responsibilities, and effectiveness. Data was analyzed and reported descriptively. RESULTS: We identified 123 studies, and included four. All were low hierarchy (highest being one level III_2 study). Commonly reported conditions were rheumatoid arthritis and ankylosing spondylitis. Information was provided on activities of role extension, such as triaging patients, monitoring and recommending changes to medications, referring to other health and medical professionals, and ordering and interpreting imaging. There was blurring between ESP and non-ESP roles. No study reported measures of effectiveness. CONCLUSION: There are descriptors of ESP physiotherapy activities, but no evidence of effectiveness of ESP physiotherapy in managing patients with inflammatory arthropathies.