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Maen Hussein,1 Marina Maglakelidze,2 Donald A Richards,3 Marielle Sabatini,4 Todd A Gersten,5 Keith Lerro,6 Ivan Sinielnikov,7 Alexander Spira,8,9 Yili Pritchett,10 Joyce M Antal,10 Rajesh Malik,10 J Thaddeus Beck11 1Florida Cancer Specialists, Leesburg, FL, USA; 2LLC Arensia Exploratory Medicine, Tbilisi, Georgia; 3Texas Oncology-Tyler, US Oncology Research, Tyler, TX, USA; 4Saint Leon Hospital, Bayonne, France; 5Florida Cancer Specialists, West Palm Beach, FL, USA; 6Regional Medical Oncology Center, Wilson, NC, USA; 7Volyn Regional Oncology Center, Lutsk, Ukraine; 8Virginia Cancer Specialists, Fairfax, VA, USA; 9US Oncology Research, The Woodlands, TX, USA; 10G1 Therapeutics, Inc., Research Triangle Park, NC, USA; 11Highlands Oncology Group, Fayetteville, AR, USACorrespondence: Maen HusseinFlorida Cancer Specialists, Leesburg, FL, USATel +1 352-787-9448Email mhussein@flcancer.comPurpose: Trilaciclib is an intravenous cyclin-dependent kinase 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression (CIM) by protecting hematopoietic stem and progenitor cells and immune system function from chemotherapy-induced damage (myeloprotection). Here, we investigated the myeloprotective effects of trilaciclib among patients at increased risk of CIM.Patients and Methods: Data were pooled from three randomized, double-blind, placebo-controlled, phase 2 clinical studies of trilaciclib administered prior to chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Myeloprotective outcomes were evaluated in patient subgroups based on age (< 65 or ≥ 65 years), risk of chemotherapy-induced febrile neutropenia (FN), and risk of anemia or red blood cell (RBC) transfusions. For the FN and anemia analyses, risk factors were identified from published literature and used to classify patients into FN and anemia risk categories. Subgroup analysis based on age was also performed on patient reported outcome (PRO) measures.Results: In total, 123 patients received trilaciclib and 119 patients received placebo. Myeloprotective benefits of trilaciclib were observed regardless of age, with greater effects observed among patients aged ≥ 65 years. Across FN risk factors and categories, trilaciclib had beneficial effects on neutrophil-related endpoints vs placebo, with greater effects observed in patients at higher risk of FN. Effects on RBC-related endpoints favored trilaciclib vs placebo, regardless of anemia risk factors and categories. Improvements in PROs with trilaciclib were observed irrespective of age group, but with greater improvements and less deterioration from baseline observed in older patients.Conclusion: By both decreasing the incidence of CIM and improving quality of life, trilaciclib has the potential to allow patients receiving chemotherapy for ES-SCLC, including patients who are older or more vulnerable to CIM, to receive chemotherapy on schedule and at standard-of-care doses, and to improve the experience for patients receiving chemotherapy to treat ES-SCLC.Clinical Trial Numbers: NCT02499770; NCT03041311; NCT02514447.Keywords: trilaciclib, myelosuppression, myeloprotection, myelopreservation, chemotherapy, small cell lung cancer

In a guest editorial in this journal, Rahm Hallberg [Rahm Hallberg, I., 2006. Challenges for future nursing research: providing evidence for health-care practice. International Journal of Nursing Studies 43, 923-927] called for research which has greater explanatory power to determine the effectiveness of nursing interventions. In this paper we critique the suggestion made by the evidence-based nursing movement that randomisation per se is the principal route to better quality nursing research. In contrast, we evaluate the new CONSORT criteria for pragmatic RCTs, which assess the quality of strategies to reduce selection, performance, attrition and detection biases, allowing many different types of comparative studies to be covered by application of the checklist. We propose that randomisation alone is a necessary but insufficient strategy and that nursing researchers rise to Rahm Hallberg's challenge by adopting the extended criteria to assist in the critical appraisal, design and reporting of all experimental research in nursing. [ABSTRACT FROM AUTHOR]

BACKGROUND: LY293111 (LY) is a novel oral anticancer agent with leukotriene B4 receptor antagonist and peroxisome proliferator-activated receptor gamma agonist properties, producing promising results alone and in combination with gemcitabine in pancreatic cancer xenograft models. A phase I study proved that the combination (gemcitabine plus LY) is safe and well tolerated. PATIENTS AND METHODS: Chemotherapy-naive patients with histologically confirmed locally advanced or metastatic adenocarcinoma of the pancreas were randomly assigned to gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and continuously administered LY 600 mg twice daily or gemcitabine 1000 mg/m on days 1, 8, and 15 of a 28-day cycle and daily oral placebo. Arms were balanced for Eastern Cooperative Oncology Group performance status and disease stage. The primary end point was 6-month survival; secondary objectives include response rate (RR), progression-free survival, and overall survival. RESULTS: Six-month survival was not different between groups (P>0.2, 1-sided); progression-free survival and RR were not different (P>0.05, 2-sided). RR was also not impacted. LY did not increase grades 3-4 hematologic toxicities, but was associated with a trend toward more, grades 3-4 diarrhea. CONCLUSIONS: These results do not demonstrate any benefit to adding LY to gemcitabine in unpretreated patients with advanced pancreatic carcinoma. [ABSTRACT FROM AUTHOR]

The randomised controlled trial (RCT) is at the heart of the evidence-based medicine movement and by implication should also be central to evidence-based nursing. One objection to RCTs in nursing science is that nursing is too complex an activity to be subjected to a carefully controlled experimental paradigm. We suggest that this argument is false and use examples from complex interventions research in nursing and experimental laboratory methods to demonstrate that RCTs can bring much needed clarity to the search for nursing knowledge. [ABSTRACT FROM AUTHOR]

Although the primary cause of constrictive pericarditis is entirely different to that of restrictive cardiomyopathy, the two often present with very similar clinical findings. As such, making the distinction between the two is a diagnostic challenge. We report a case that highlights how tissue Doppler imaging may simplify the distinction between pericardial constriction and myocardial restriction. [ABSTRACT FROM AUTHOR]

BACKGROUND: Collaborative care is an effective intervention for depression which includes both organizational and patient-level intervention components. The effect in the UK is unknown, as is whether cluster- or patient-randomization would be the most appropriate design for a Phase III clinical trial.MethodWe undertook a Phase II patient-level randomized controlled trial in primary care, nested within a cluster-randomized trial. Depressed participants were randomized to 'collaborative care' - case manager-coordinated medication support and brief psychological treatment, enhanced specialist and GP communication - or a usual care control. The primary outcome was symptoms of depression (PHQ-9). RESULTS: We recruited 114 participants, 41 to the intervention group, 38 to the patient randomized control group and 35 to the cluster-randomized control group. For the intervention compared to the cluster control the PHQ-9 effect size was 0.63 (95% CI 0.18-1.07). There was evidence of substantial contamination between intervention and patient-randomized control participants with less difference between the intervention group and patient-randomized control group (-2.99, 95% CI -7.56 to 1.58, p=0.186) than between the intervention and cluster-randomized control group (-4.64, 95% CI -7.93 to -1.35, p=0.008). The intra-class correlation coefficient for our primary outcome was 0.06 (95% CI 0.00-0.32). CONCLUSIONS: Collaborative care is a potentially powerful organizational intervention for improving depression treatment in UK primary care, the effect of which is probably partly mediated through the organizational aspects of the intervention. A large Phase III cluster-randomized trial is required to provide the most methodologically accurate test of these initial encouraging findings. [ABSTRACT FROM AUTHOR]

This paper's aim is to draw attention to the pitfalls that novice and, sometimes, experienced researchers fall into when undertaking quantitative data analysis in the health and social sciences, and to offer some guidance as to how such pitfalls might be avoided.Many health and social science students are routinely instructed that the procedure for undertaking data analysis in quantitative research is as follows: specify hypotheses; collect data and enter it into a computerised statistical package; run various statistical procedures; examine the computer outputs for p-values that are statistically significant. If significant differences are found, jubilation often exists because statistically significant results are deemed to be a clear indicator that something worthwhile (and publishable) has been discovered. This paper argues that this approach has two major oversights: a failure to explore the raw data prior to analysis and an overdependence on p-values. Both of these oversights are routinely present in much health and social-science research, and both create problems for scientific rigour.Researchers need to exercise caution ('look before you leap') and prudence ('don't put all your eggs in one basket') when undertaking quantitative data analyses. Caution demands that, prior to full data analysis, researchers employ procedures such as data cleaning, data screening and exploratory data analysis. Prudence demands that researchers see p-values for their true worth, which exists only within the context of statistical theory, confidence intervals, effect sizes and the absolute meaning of statistical significance. [ABSTRACT FROM AUTHOR]

Recent policy statements that address the quality of care provided by acute mental health services have highlighted an urgent need for specialist nurse education and training. However, examples of how to design and implement such training initiatives are sparse. Drawing on recent experience of developing an innovative training programme for acute psychiatric settings, this paper seeks to examine some of the key issues associated with current training provision for acute inpatient mental health workers. The methodological and practical concerns surrounding this type of initiative are discussed with the main aspects of programme content, service user participation, team training and organizational challenges being explored. Resulting from this work, several recommendations regarding the content, organization and delivery of future training initiatives are made. [ABSTRACT FROM AUTHOR]

Nursing attitudes towards acute mental health care: development of a measurement toolAim. This paper reports the development, piloting and validation of a tool to measure attitudes for use with nursing staff working in acute mental health care units. Background. The quality of care provided for service users in acute mental health care has come under both scrutiny and severe criticism. The attitudes of staff working in these environments have been cited as a contributory factor in poor care. No measure of attitudes specific to acute mental health has been reported. Methods. A 64-question measure was constructed and distributed to a sample of qualified and unqualified nurses drawn from seven mental health care units in the North of England. Exploratory factor analysis and a number of other statistical tests were performed to validate the questionnaire. Results. Preliminary analysis reduced the original 64 questions to 37. Five components were retained, accounting for 42% of the variance, and the five rotated factors were identified. The resultant 'Attitudes Towards Acute Mental Health Scale' (ATAMHS) achieved good internal reliability, with a Cronbach's alpha of 0.72. Conclusion. The construction and validation of the ATAMHS measure will enable improved understanding of the attitudes of nursing staff working in acute mental health care settings to occur. This measure is available for use in a clinical area of nursing in which attitude change is of fundamental importance for future development of care. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nurse telephone triage is a popular way of managing workload in primary care and has been shown to be as safe as general practitioner (GP)-delivered alternatives. No studies have tested a routine method of assessing the quality of decision-making by triage nurses in primary care. AIMS: The aim of this paper is to describe a study to evaluate accuracy and utility of audiotaping telephone consultations to assess the quality of decisions made by practice nurses triaging same day appointment requests in routine practice. METHOD: An observational study was carried out using external assessment by GPs and nurse practitioners of triage quality in 218 audiotaped nurse telephone triage consultations. RESULTS: There were high levels of agreement between triage nurses and assessors on identifying the presenting problem. However, there were only moderate levels of agreement between GPs and nurse assessors both on level of information sought (kappa = 0.434) and appropriateness of outcome (kappa = 0.614). Assessors rated information-gathering as poor in 19.3% of calls (95% confidence interval 14.6 to 25.0), and seven (3.2%) consultations were rated as potentially dangerous (95% confidence interval 1.6 to 6.5). A 1% sample of all consultations would have a probability of 0.48 of identifying unsafe consultations and 0.99 probability of identifying consultations with poor information-gathering. CONCLUSIONS: External assessment of triage quality may be of only moderate accuracy and reliability. Nonetheless, considerable information can be gleaned from assessing audiotapes to assess consultation quality. Even where nurses are generally highly skilled and competent, a 1% review of triage consultations would be sufficient to identify their information-gathering learning needs in relation to patients' presenting problems. Audio-taped consultations could be an important part of clinical governance strategies. [ABSTRACT FROM AUTHOR]

This study compares the effects of the nursing process and traditional care in a patient population where the environment, nurses, other multidisciplinary team members and the nursing model were the same for two patient groups. Both groups were nursed using traditional therapeutic community techniques. One group also received care using a nursing process approach. Patients in the nursing process group did not feel nurses were significantly more therapeutic nor were they more satisfied with their care. [ABSTRACT FROM AUTHOR]

1 The anti-hypertensive effects of labetalol have been compared and contrasted with other groups of anti-hypertensive drugs in this review of the published literature. 2 The data show that the pharmacological and haemodynamic profile of labetalol in man is distinctly different from that of other specific anti-hypertensive agents; namely the properties of competitive alpha-and beta-adrenoceptor blockade leading to haemodynamic effects of reduced blood pressure and peripheral vascular resistance with little accompanying changes in resting heart rate or cardiac output. 3 The anti-hypertensive effects of labetalol are dose related. In fixed dose comparative studies equivalent anti- hypertensive effects to those of labetalol have been shown for individual drugs of the beta-adrenoceptor-blocking and diuretic groups. In dose titration studies, equivalent anti-hypertensive effects at given doses of labetalol have been demonstrated for drugs of the following types: beta-adrenoceptor blockers, beta-blockers plus diuretics, methyldopa, adrenergic neurone blockers and the combination of beta-blockers plus a peripheral vasodilator. 4 Comparing side-effect liabilities, it is clear that quantitatively labetalol produces no greater burden of side-effects than drugs of the beta-adrenoceptor- blocking group. Qualitative differences, however, do exist; in particular, symptomatic postural hypotension is dose related and is more likely to occur when excessive doses (greater than 2 g daily) are used. [ABSTRACT FROM AUTHOR]

Melanoma is the most common form of cardiac metastases. Surgical excision has been shown to be an effective palliative measure. This requires detailed definition of cardiac anatomy in relation to the tumour. Two-dimensional (2D), three-dimensional (3D) transthoracic (TTE) and transoesophageal echocardiography (TEE), spiral computerised tomography (CT) and magnetic resonance imaging (MRI) have all been described in aiding surgical planning for excision of cardiac tumours. In this case report, 3D-TTE provided excellent anatomical definition for surgical planning of a large right atrial melanoma precluding the need for more invasive and expensive investigations. [ABSTRACT FROM AUTHOR]

Abstract Background Recent years have seen an increase in primary care workload, especially following the introduction of a new General Medical Services contract in 2004. Telephone triage and telephone consultation with patients seeking health care represent initiatives aimed at improving access to care. Some evidence suggests that such approaches may be feasible but conclusions regarding GP workload, cost, and patients’ experience of care, safety, and health status are equivocal. The ESTEEM trial aims to assess the clinical- and cost-effectiveness of nurse-led computer-supported telephone triage and GP-led telephone triage, compared to usual care, for patients requesting same-day consultations in general practice. Methods/design ESTEEM is a pragmatic, multi-centre cluster randomised clinical trial with patients randomised at practice level to usual care, computer decision-supported nurse triage, or GP-led triage. Following triage of 350–550 patients per practice we anticipate estimating and comparing total primary care workload (volume and time), the economic cost to the NHS, and patient experience of care, safety, and health status in the 4-week period following the index same-day consultation request across the three trial conditions. We will recruit all patients seeking a non-emergency same-day appointment in primary care. Patients aged 12.0–15.9 years and temporary residents will be excluded from the study. The primary outcome is the number of healthcare contacts taking place in the 4-week period following (and including) the index same-day consultation request. A range of secondary outcomes will be examined including patient flow, primary care NHS resource use, patients’ experience of care, safety, and health status. The estimated sample size required is 3,751 patients (11,253 total) in each of the three trial conditions, to detect a mean difference of 0.36 consultations per patient in the four week follow-up period between either intervention group and usual care 90% power, 5% alpha, and an estimated intracluster correlation coefficient ICC of 0.05. The primary analysis will be based on the intention-to-treat principle and take the form of a random effects regression analysis taking account of the hierarchical nature of the study design. Statistical models will allow for adjustment for practice level minimisation variables and patient-level baseline covariates shown to differ at baseline. Trial registration Current Controlled Trials ISCRTN20687662

Abstract Background In the United Kingdom, clinical guidelines recommend that services for depression and anxiety should be structured around a stepped care model, where patients receive treatment at different 'steps,' with the intensity of treatment (i.e., the amount and type) increasing at each step if they fail to benefit at previous steps. There are very limited data available on the implementation of this model, particularly on the intensity of psychological treatment at each step. Our objective was to describe patient pathways through stepped care services and the impact of this on patient flow and management. Methods We recorded service design features of four National Health Service sites implementing stepped care (e.g., the types of treatments available and their links with other treatments), together with the actual treatments received by individual patients and their transitions between different treatment steps. We computed the proportions of patients accessing, receiving, and transiting between the various steps and mapped these proportions visually to illustrate patient movement. Results We collected throughput data on 7,698 patients referred. Patient pathways were highly complex and very variable within and between sites. The ratio of low (e.g., self-help) to high-intensity (e.g., cognitive behaviour therapy) treatments delivered varied between sites from 22:1, through 2.1:1, 1.4:1 to 0.5:1. The numbers of patients allocated directly to high-intensity treatment varied from 3% to 45%. Rates of stepping up from low-intensity treatment to high-intensity treatment were less than 10%. Conclusions When services attempt to implement the recommendation for stepped care in the National Institute for Health and Clinical Excellence guidelines, there were significant differences in implementation and consequent high levels of variation in patient pathways. Evaluations driven by the principles of implementation science (such as targeted planning, defined implementation strategies, and clear activity specification around service organisation) are required to improve evidence on the most effective, efficient, and acceptable stepped care systems.

Abstract Background Integrating the best available evidence into program standards is essential if system-wide improvements in the delivery of community-based mental health services are to be achieved. Since the beginning of the Assertive Community Treatment (ACT) program movement, program standards have included a role for the community. In particular, ACT program standards have sought to ensure that members of the local community are involved in governance and that former clients participate in service delivery as "Peer Support Specialists". This paper reports on the extent to which ACT program standards related to community participation have been implemented and identifies barriers to full compliance. Methods Qualitative and quantitative data were collected through a telephone survey of ACT Program Coordinators in Ontario, Canada, using a census sample of the existing 66 ACT programs. A thematic approach to content analysis was used to analyze respondents' qualitative comments. Quantitative data were analyzed using SPSS 16.0 and included means, frequencies, independent t-tests and Pearson Correlations. Results An 85% response rate was achieved. Of the 33 program standards, the two that received the lowest perceived compliance ratings were the two standards directly concerning community participation. Specifically, the standard to have a functioning Community Advisory Body and the standard requiring the inclusion of a Peer Support Specialist. The three major themes that emerged from the survey data with respect to the barriers to fully implementing the Community Advisory Body were: external issues; standard related issues; and, organizational/structural related issues. The three major themes concerning barriers to implementing the Peer Support Specialist role were: human resource related issues; organizational/structural related issues; and, standard related issues. Conclusions The reasons for low compliance of ACT programs with community participation standards are complex and are tied to structural and human resources barriers (both internal and external to the ACT programs) as well as to the requirements of the standards themselves. In order for improvements to the mental health system to be achieved there is a need to identify and address these barriers. Failure to do so will result in less than optimal client, family and economic efficiency outcomes.

Abstract Background Depression accounts for the greatest burden of disease among all mental health problems, and is expected to become the second-highest amongst all general health problems by 2020. By the age of 75, 1 in 7 older people meet formal diagnostic criteria for depression. Efforts to ameliorate the burden of illness and personal suffering associated with depression in older people have focussed on those with more severe depressive syndromes. Less attention has been paid to those with mild disorders/sub-threshold depressive syndromes but these patients also suffer impairments in their quality of life and level of functioning. Methods/Design The CASPER study has been designed to assemble an epidemiological cohort of people over 75 years of age (the CASPER cohort), from which we will identify those eligible to participate in a trial of collaborative care for sub-threshold depression (the CASPER trial). We aim to undertake a pragmatic randomised controlled multi-centre trial evaluating the effectiveness and cost-effectiveness of collaborative care; a low intensity psychological intervention in addition to usual general practitioner care versus usual general practitioner care alone. General practitioners from practices based in the North of England will be asked to identify potentially eligible patients over the age of 75 years. Patients will be sent a letter inviting them to participate in the study. We aim to recruit approximately 540 participants for the CASPER trial. A diagnostic interview will be carried out to ascertain trial eligibility with the major depressive episode module of the Mini International Neuropsychiatric Interview (M.I.N.I.), eligible participants randomised to either the intervention or usual care. The primary outcome will be measured with the Patient Health Questionnaire-9 (PHQ-9) and additional quality of life measures will be collected. Data will be collected at baseline, 4 and 12 months for both trial and cohort participants. Trial Registration ISRCTN: ISRCTN02202951

Abstract Background Prediction of the location of culprit lesions responsible for ST-segment elevation myocardial infarctions may allow for prevention of these events. A retrospective analysis of coronary artery motion (CAM) was performed on coronary angiograms of 20 patients who subsequently had ST-segment elevation myocardial infarction treated by primary or rescue angioplasty and an equal number of age and sex matched controls with normal angiograms. Findings There was no statistically significant difference between the frequency of CAM types of the ST-segment elevation acute myocardial infarction and control patients (p = 0.97). The compression type of CAM is more frequent in the proximal and mid segments of all three coronary arteries. No statistically significant difference was found when the frequency of the compression type of CAM was compared between the ST-segment elevation acute myocardial infarction and control patients for the individual coronary artery segments (p = 0.59). Conclusion The proportion of the compression type of coronary artery motion for individual artery segments is not different between patients who have subsequent ST-segment elevation myocardial infarctions and normal controls.

Abstract Background There is a considerable evidence base for 'collaborative care' as a method to improve quality of care for depression, but an acknowledged gap between efficacy and implementation. This study utilises the Normalisation Process Model (NPM) to inform the process of implementation of collaborative care in both a future full-scale trial, and the wider health economy. Methods Application of the NPM to qualitative data collected in both focus groups and one-to-one interviews before and after an exploratory randomised controlled trial of a collaborative model of care for depression. Results Findings are presented as they relate to the four factors of the NPM (interactional workability, relational integration, skill-set workability, and contextual integration) and a number of necessary tasks are identified. Using the model, it was possible to observe that predictions about necessary work to implement collaborative care that could be made from analysis of the pre-trial data relating to the four different factors of the NPM were indeed borne out in the post-trial data. However, additional insights were gained from the post-trial interview participants who, unlike those interviewed before the trial, had direct experience of a novel intervention. The professional freedom enjoyed by more senior mental health workers may work both for and against normalisation of collaborative care as those who wish to adopt new ways of working have the freedom to change their practice but are not obliged to do so. Conclusions The NPM provides a useful structure for both guiding and analysing the process by which an intervention is optimized for testing in a larger scale trial or for subsequent full-scale implementation.