CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.

BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.

Smartphone ECG for evaluation of STEMI: Results of the ST LEUIS Pilot Study

© 2015 Elsevier Inc. All rights reserved.Background 12-lead ECG is a critical component of initial evaluation of cardiac ischemia, but has traditionally been limited to large, dedicated equipment in medical care environments. Smartphones provide a potential alternative platform for the extension of ECG to new care settings and to improve timeliness of care. Objective To gain experience with smartphone electrocardiography prior to designing a larger multicenter study evaluating standard 12-lead ECG compared to smartphone ECG. Methods 6 patients for whom the hospital STEMI protocol was activated were evaluated with traditional 12-lead ECG followed immediately by a smartphone ECG using right (VnR) and left (VnL) limb leads for precordial grounding. The AliveCor™ Heart Monitor was utilized for this study. All tracings were taken prior to catheterization or immediately after revascularization while still in the catheterization laboratory. Results The smartphone ECG had excellent correlation with the gold standard 12-lead ECG in all patients. Four out of six tracings were judged to meet STEMI criteria on both modalities as determined by three experienced cardiologists, and in the remaining two, consensus indicated a non-STEMI ECG diagnosis. No significant difference was noted between VnR and VnL. Conclusions Smartphone based electrocardiography is a promising, developing technology intended to increase availability and speed of electrocardiographic evaluation. This study confirmed the potential of a smartphone ECG for evaluation of acute ischemia and the feasibility of studying this technology further to define the diagnostic accuracy, limitations and appropriate use of this new technology.

A new instrument for measuring anticoagulation-related quality of life: development and preliminary validation.

BACKGROUND: Anticoagulation can reduce quality of life, and different models of anticoagulation management might have different impacts on satisfaction with this component of medical care. Yet, to our knowledge, there are no scales measuring quality of life and satisfaction with anticoagulation that can be generalized across different models of anticoagulation management. We describe the development and preliminary validation of such an instrument - the Duke Anticoagulation Satisfaction Scale (DASS). METHODS: The DASS is a 25-item scale addressing the (a) negative impacts of anticoagulation (limitations, hassles and burdens); and (b) positive impacts of anticoagulation (confidence, reassurance, satisfaction). Each item has 7 possible responses. The DASS was administered to 262 patients currently receiving oral anticoagulation. Scales measuring generic quality of life, satisfaction with medical care, and tendency to provide socially desirable responses were also administered. Statistical analysis included assessment of item variability, internal consistency (Cronbach's alpha), scale structure (factor analysis), and correlations between the DASS and demographic variables, clinical characteristics, and scores on the above scales. A follow-up study of 105 additional patients assessed test-retest reliability. RESULTS: 220 subjects answered all items. Ceiling and floor effects were modest, and 25 of the 27 proposed items grouped into 2 factors (positive impacts, negative impacts, this latter factor being potentially subdivided into limitations versus hassles and burdens). Each factor had a high degree of internal consistency (Cronbach's alpha 0.78-0.91). The limitations and hassles factors consistently correlated with the SF-36 scales measuring generic quality of life, while the positive psychological impact scale correlated with age and time on anticoagulation. The intra-class correlation coefficient for test-retest reliability was 0.80. CONCLUSIONS: The DASS has demonstrated reasonable psychometric properties to date. Further validation is ongoing. To the degree that dissatisfaction with anticoagulation leads to decreased adherence, poorer INR control, and poor clinical outcomes, the DASS has the potential to help identify reasons for dissatisfaction (and positive satisfaction), and thus help to develop interventions to break this cycle. As an instrument designed to be applicable across multiple models of anticoagulation management, the DASS could be crucial in the scientific comparison between those models of care.

Future requirements for and supply of ophthalmologists for an aging population in Singapore.

BACKGROUND: Singapore's population, as that of many other countries, is aging; this is likely to lead to an increase in eye diseases and the demand for eye care. Since ophthalmologist training is long and expensive, early planning is essential. This paper forecasts workforce and training requirements for Singapore up to the year 2040 under several plausible future scenarios. METHODS: The Singapore Eye Care Workforce Model was created as a continuous time compartment model with explicit workforce stocks using system dynamics. The model has three modules: prevalence of eye disease, demand, and workforce requirements. The model is used to simulate the prevalence of eye diseases, patient visits, and workforce requirements for the public sector under different scenarios in order to determine training requirements. RESULTS: Four scenarios were constructed. Under the baseline business-as-usual scenario, the required number of ophthalmologists is projected to increase by 117% from 2015 to 2040. Under the current policy scenario (assuming an increase of service uptake due to increased awareness, availability, and accessibility of eye care services), the increase will be 175%, while under the new model of care scenario (considering the additional effect of providing some services by non-ophthalmologists) the increase will only be 150%. The moderated workload scenario (assuming in addition a reduction of the clinical workload) projects an increase in the required number of ophthalmologists of 192% by 2040. Considering the uncertainties in the projected demand for eye care services, under the business-as-usual scenario, a residency intake of 8-22 residents per year is required, 17-21 under the current policy scenario, 14-18 under the new model of care scenario, and, under the moderated workload scenario, an intake of 18-23 residents per year is required. CONCLUSIONS: The results show that under all scenarios considered, Singapore's aging and growing population will result in an almost doubling of the number of Singaporeans with eye conditions, a significant increase in public sector eye care demand and, consequently, a greater requirement for ophthalmologists.

Clinical utility of a Web-enabled risk-assessment and clinical decision support program.

PURPOSE: Risk-stratified guidelines can improve quality of care and cost-effectiveness, but their uptake in primary care has been limited. MeTree, a Web-based, patient-facing risk-assessment and clinical decision support tool, is designed to facilitate uptake of risk-stratified guidelines. METHODS: A hybrid implementation-effectiveness trial of three clinics (two intervention, one control). PARTICIPANTS: consentable nonadopted adults with upcoming appointments. PRIMARY OUTCOME: agreement between patient risk level and risk management for those meeting evidence-based criteria for increased-risk risk-management strategies (increased risk) and those who do not (average risk) before MeTree and after. MEASURES: chart abstraction was used to identify risk management related to colon, breast, and ovarian cancer, hereditary cancer, and thrombosis. RESULTS: Participants = 488, female = 284 (58.2%), white = 411 (85.7%), mean age = 58.7 (SD = 12.3). Agreement between risk management and risk level for all conditions for each participant, except for colon cancer, which was limited to those <50 years of age, was (i) 1.1% (N = 2/174) for the increased-risk group before MeTree and 16.1% (N = 28/174) after and (ii) 99.2% (N = 2,125/2,142) for the average-risk group before MeTree and 99.5% (N = 2,131/2,142) after. Of those receiving increased-risk risk-management strategies at baseline, 10.5% (N = 2/19) met criteria for increased risk. After MeTree, 80.7% (N = 46/57) met criteria. CONCLUSION: MeTree integration into primary care can improve uptake of risk-stratified guidelines and potentially reduce "overuse" and "underuse" of increased-risk services.Genet Med 18 10, 1020-1028.

Utility of a molecular prescreening program in advanced colorectal cancer for enrollment on biomarker-selected clinical trials.

BACKGROUND: Incorporation of multiple enrichment biomarkers into prospective clinical trials is an active area of investigation, but the factors that determine clinical trial enrollment following a molecular prescreening program have not been assessed. PATIENTS AND METHODS: Patients with 5-fluorouracil-refractory metastatic colorectal cancer at the MD Anderson Cancer Center were offered screening in the Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC) program to identify eligibility for companion phase I or II clinical trials with a therapy targeted to an aberration detected in the patient, based on testing by immunohistochemistry, targeted gene sequencing panels, and CpG island methylation phenotype assays. RESULTS: Between August 2010 and December 2013, 484 patients were enrolled, 458 (95%) had a biomarker result, and 157 (32%) were enrolled on a clinical trial (92 on biomarker-selected and 65 on nonbiomarker selected). Of the 458 patients with a biomarker result, enrollment on biomarker-selected clinical trials was ninefold higher for predefined ATTACC-companion clinical trials as opposed to nonpredefined biomarker-selected clinical trials, 17.9% versus 2%, P < 0.001. Factors that correlated positively with trial enrollment in multivariate analysis were higher performance status, older age, lack of standard of care therapy, established patient at MD Anderson, and the presence of an eligible biomarker for an ATTACC-companion study. Early molecular screening did result in a higher rate of patients with remaining standard of care therapy enrolling on ATTACC-companion clinical trials, 45.1%, in contrast to nonpredefined clinical trials, 22.7%; odds ratio 3.1, P = 0.002. CONCLUSIONS: Though early molecular prescreening for predefined clinical trials resulted in an increase rate of trial enrollment of nonrefractory patients, the majority of patients enrolled on clinical trials were refractory to standard of care therapy. Within molecular prescreening programs, tailoring screening for preidentified and open clinical trials, temporally linking screening to treatment and optimizing both patient and physician engagement are efforts likely to improve enrollment on biomarker-selected clinical trials. CLINICAL TRIALS NUMBER: The study NCT number is NCT01196130.

Selection of Postacute Stroke Rehabilitation Facilities: A Survey of Discharge Planners From the Northeast Cerebrovascular Consortium (NECC) Region.

The process of determining the level of care and specific postacute care facility for stroke patients has not been adequately studied. The objective of this study was to better understand the factors that influence postacute care decisions by surveying stroke discharge planners. Requests were sent to discharge planners at 471 hospitals in the Northeast United States to complete an online survey regarding the factors impacting the selection of postacute care. Seventy-seven (16%) discharge planners completed the online survey. Respondents were mainly nurses and social workers and 73% reported ≥20 years healthcare experience. Patients and families were found to be significantly more influential than physicians (P < 0.001) and other clinicians (P = 0.04) in influencing postdischarge care. Other clinicians were significantly more influential than physicians (P < 0.001). Insurance and quality of postacute care were the factors likely to most affect the selection of postacute care facility. Insurance was also identified as the greatest barrier in the selection of level of postacute care (70%; P < 0.001) and specific postacute care facility (46%; P = 0.02). More than half reported that pressure to discharge patients quickly impacts a patients' final destination. Nonclinical factors are perceived by discharge planners to have a major influence on postacute stroke care decision making.

Evaluation of the quality of the management of cancer of the corpus uteri-Selection of relevant quality indicators and implementation in Belgium

Objective Describe the methodology and selection of quality indicators (QI) to be implemented in the EFFECT (EFFectiveness of Endometrial Cancer Treatment) project. EFFECT aims to monitor the variability in Quality of Care (QoC) of uterine cancer in Belgium, to compare the effectiveness of different treatment strategies to improve the QoC and to check the internal validity of the QI to validate the impact of process indicators on outcome. Methods A QI list was retrieved from literature, recent guidelines and QI databases. The Belgian Healthcare Knowledge Center methodology was used for the selection process and involved an expert's panel rating the QI on 4 criteria. The resulting scores and further discussion resulted in a final QI list. An online EFFECT module was developed by the Belgian Cancer Registry including the list of variables required for measuring the QI. Three test phases were performed to evaluate the relevance, feasibility and understanding of the variables and to test the compatibility of the dataset. Results 138 QI were considered for further discussion and 82 QI were eligible for rating. Based on the rating scores and consensus among the expert's panel, 41 QI were considered measurable and relevant. Testing of the data collection enabled optimization of the content and the user-friendliness of the dataset and online module. Conclusions This first Belgian initiative for monitoring the QoC of uterine cancer indicates that the previously used QI selection methodology is reproducible for uterine cancer. The QI list could be applied by other research groups for comparison. © 2013 Elsevier Inc.

Seroprotection against tetanus in patients attending an emergency department in Belgium and evaluation of a bedside immunotest.

BACKGROUND: In most emergency departments, tetanus prophylaxis currently relies on vaccination history. Bedside evaluation of tetanus immunity may improve this process. OBJECTIVES: (i) To determine the seroprevalence of tetanus immunity; (ii) to evaluate the accuracy of vaccination history in assessing tetanus immunity; (iii) to identify factors predictive of seroprotection and incorrect history. METHOD: In a prospective observational study, tetanus immunity was assessed in 784 adults using Tétanos Quick Stick (TQS). A questionnaire was completed to obtain vaccination and general histories. Immunity assessed by TQS and by vaccination history were compared with anti-tetanus antibody levels measured by the enzyme-linked immunosorbent assay (seroprotection threshold >0.15 IU/ml). RESULTS: Overall, 64.2% of patients were protected according to TQS results. Four independent predictors of seroprotection were identified: young age, birthplace in Belgium, male sex and occupational medicine consultation. TQS performance was good: kappa=0.71, sensitivity 85.3%, specificity 87.2%, positive predictive value 92.1% and negative predictive value 77.2%. Seven hundred and sixty-two participants responded to the vaccination history: 23.4% said they were protected, 22.1% that they were not and 54.5% did not know. History performance was poor: kappa=0.27, sensitivity 60.3%, specificity 73.3%, positive predictive value 81.8% and negative predictive value 45.8%. Compared with history, TQS offered a significantly better sensitivity, negative and positive predictive values, but specificity was similar. No predictor of an incorrect history was identified. CONCLUSION: Lack of protective immunity against tetanus is frequent but poorly evaluated by history taking. Several demographic characteristics are good predictors of seroprotection. TQS could be a valuable tool in selected patients to improve tetanus prophylaxis in the emergency department.

Grandparents and parenting: towards a theory of grandparenthood

This paper explores the changing role of contemporary grandparents with many demonstrating a willingness and ability to take on parental responsibilities for their grandchildren, where they may face challenges and opportunities in difficult times. Three main forms of grand parenting are identified in the literature, those who have primary responsibility and are raising their grand children as their main carers perhaps in response to crisis situations, those who live in extended families and participate in care, and those who provide day care while the child’s parents work. The latter has increased because of the increasing frequency of divorce, single parenting and the lack of available or subsidised child care in the United Kingdom. When grandparents step into a troubled situation and attempt to offer stability and security for their grandchildren they may have to manage the combined responsibilities of family caregivers and parental figures. Grandparenthood is a tenuous role, lacking clear agreement on behaviour norms. In the culture of advice and parenting support, while care must be taken not to undermine parenting skills or make judgements about the ability to cope with the demands of childcare, an exploration of the impact on grandparents and children must be undertaken. Due to the complex web of interrelated factors the process and outcomes of care giving by grandparents is not well known in the literature. It is proposed therefore that it is timely for research to be undertaken to explore and develop a theory of Grandparenthood.

Tied to the job: affective and relational components of nurse retention

Paper investigates whether affective and relational components of nurses' experience of work have a significant impact on their intentions to leave either the job or the nursing profession in models that control for other factors (sociodemographic, work conditions, perceptions of quality of care) that are known to affect career decisions. [Abridged Abstract]

Addressing Bed Costs for the Elderly: A New Methodology for Modelling Patient Outcomes and Length of Stay

The proportion of elderly in the population has dramatically increased and will continue to do so for at least the next 50 years. Medical resources throughout the world are feeling the added strain of the increasing proportion of elderly in the population. The effective care of elderly patients in hospitals may be enhanced by accurately modelling the length of stay of the patients in hospital and the associated costs involved. This paper examines previously developed models for patient length of stay in hospital and describes the recently developed conditional phase-type distribution (C-Ph) to model patient duration of stay in relation to explanatory patient variables. The Clinics data set was used to demonstrate the C-Ph methodology. The resulting model highlighted a strong relationship between Barthel grade, patient outcome and length of stay showing various groups of patient behaviour. The patients who stay in hospital for a very long time are usually those that consume the largest amount of hospital resources. These have been identified as the patients whose resulting outcome is transfer. Overall, the majority of transfer patients spend a considerably longer period of time in hospital compared to patients who die or are discharged home. The C-Ph model has the potential for considering costs where different costs are attached to the various phases or subgroups of patients and the anticipated cost of care estimated in advance. It is hoped that such a method will lead to the successful identification of the most cost effective case-mix management of the hospital ward.

Identity issues for looked after children with no knowledge of their origins - Implications for research and practice

In the area of child care policy and practice, the benefits for children who are separated from their birth parents of maintaining some form of connection with their family of origin is now widely accepted. The arguments in support of this are found mainly in research concerning adoption and stem from four inter-related themes: children's rights to know of their heritage and background; parents' rights to information about the well-being of their children; the benefits of having knowledge about origins; and concerns about the impact of not knowing. The effects on the developing identities of those who, for various reasons, are unlikely ever to know the details of their birth parent(s) is an under-researched issue. Karen Winter and Olivia Cohen use a case study to illustrate some of the gaps concerning knowledge in this area. They argue that there is much to be learnt from the development of research projects which have as their focus the accounts of children and young people, from a wide range of care arrangements, regarding identity issues where they have no connections with or knowledge about their birth parent(s).

A prospective clinical trial of a real-time polymerase chain reaction assay for the diagnosis of candidemia in nonneutropenic, critically ill adults

Background. Invasive Candida infection among nonneutropenic, critically ill adults is a clinical problem that has received increasing attention in recent years. Poor performance of extant diagnostic modalities has promoted risk-based, preemptive prescribing in view of the poor outcomes associated with inadequate or delayed antifungal therapy; this risks unnecessary overtreatment. A rapid, reliable diagnostic test could have a substantial impact on therapeutic practice in this patient population.

Methods. Three TaqMan-based real-time polymerase chain reaction assays were developed that are capable of detecting the main medically important Candida species, categorized according to the likelihood of fluconazole susceptibility. Assay 1 detected Candida albicans, Candida parapsilosis, Candida tropicalis, and Candida dubliniensis. Assays 2 and 3 detected Candida glabrata and Candida krusei, respectively. The clinical performance of these assays, applied to serum, was evaluated in a prospective trial of nonneutropenic adults in a single intensive care unit.

Results. In all, 527 specimens were obtained from 157 participants. All 3 assays were run in parallel for each specimen; they could be completed within 1 working day. Of these, 23 specimens were obtained from 23 participants categorized as having proven Candida infection at the time of sampling. If a single episode of Candida famata candidemia was excluded, the estimated clinical sensitivity, specificity, and positive and negative predictive values of the assays in this trial were 90.9%, 100%, 100% and 99.8%, respectively.

Conclusions. These data suggest that the described assays perform well in this population for enhancing the diagnosis of candidemia. The extent to which they may affect clinical outcomes, prescribing practice, and cost-effectiveness of care remains to be ascertained.

Parent-offspring conflict and motivational control of brooding in an amphipod (Crustacea)

Models of parent - offspring conflict concerning levels of caregiving centre on conflict resolution by offspring control, compromise or offspring 'honest signalling' that parents use to maximize their own fitness. Recent empirical studies on motivational control of parental feeding of offspring are interpreted as supporting the latter model. Here, we examine parental care in an amphipod, Crangonyx pseudogracilis, which directs care to embryos in a brood pouch. Embryo removal and transplantation elucidated causal factors that determine levels of caregiving. In the short-term, females with all embryos removed reduced care activities, but partial embryo removal did not affect caregiving, evidence of 'unshared' parental care. In the long-term, females with all embryos removed ceased care. Thus, females have a maternal state that is maintained by stimuli from offspring. Transplantation of early/late stage embryos among females originally carrying early/late stage embryos revealed that stimuli from embryos indicate their age-dependent needs, but only modify caregiving within the constraints of a changing endogenous maternal state. Thus, we demonstrate that mothers and offspring share motivational control of care. However, we highlight the inappropriate use of motivational data in reaching conclusions about the resolution of parent - offspring conflict.