Evaluation of a training program for general ultrasound screening for developmental dysplasia of the hip in preventive child health care

Background: A research study in the Netherlands showed that general ultrasound (US) screening was cost-effective in the detection of developmental dysplasia of the hip (DDH). This study was followed by a pilot implementation study. Part of this pilot implementation study is to investigate whether professionals of the infant health care (IHC) system, with no previous US experience, would be able to perform US of the hip. Objective: This study looks at health care worker ability to classify US images into a modified Graf system. Materials and methods: After theoretical and practical training, seven nurses and physicians of the participating IHC centers reported their findings on sonographic images of 80 children. This was repeated five months later. From the two evaluation moments the intraobserver agreement and the interobserver agreement was determined. Results: The average estimated interobserver Cohen’s kappa for both sessions was for nurses 0.6 and for physicians 0.5. The second evaluation showed a decrease from an average of 4.3% missed cases per screener to 2.3% and an increase of an average of 5% false positives per screener to 9.1%. Conclusion: The inter- and intra-observer agreement is comparable to similar studies in which the participants had a professional background in US examination. The level of agreement of the trainees in the perspective of the screening process was considered sufficient for the pilot implementation project

A Discrete Event Simulation model to evaluate the treatment pathways of patients with Cataract in the United Kingdom

Background The number of people affected by cataract in the United Kingdom (UK) is growing rapidly due to ageing population. As the only way to treat cataract is through surgery, there is a high demand for this type of surgery and figures indicate that it is the most performed type of surgery in the UK. The National Health Service (NHS), which provides free of charge care in the UK, is under huge financial pressure due to budget austerity in the last decade. As the number of people affected by the disease is expected to grow significantly in coming years, the aim of this study is to evaluate whether the introduction of new processes and medical technologies will enable cataract services to cope with the demand within the NHS funding constraints. Methods We developed a Discrete Event Simulation model representing the cataract services pathways at Leicester Royal Infirmary Hospital. The model was inputted with data from national and local sources as well as from a surgery demand forecasting model developed in the study. The model was verified and validated with the participation of the cataract services clinical and management teams. Results Four scenarios involving increased number of surgeries per half-day surgery theatre slot were simulated. Results indicate that the total number of surgeries per year could be increased by 40% at no extra cost. However, the rate of improvement decreases for increased number of surgeries per half-day surgery theatre slot due to a higher number of cancelled surgeries. Productivity is expected to improve as the total number of doctors and nurses hours will increase by 5 and 12% respectively. However, non-human resources such as pre-surgery rooms and post-surgery recovery chairs are under-utilized across all scenarios. Conclusions Using new processes and medical technologies for cataract surgery is a promising way to deal with the expected higher demand especially as this could be achieved with limited impact on costs. Non-human resources capacity need to be evenly levelled across the surgery pathway to improve their utilisation. The performance of cataract services could be improved by better communication with and proactive management of patients.Peer reviewedFinal Published versio

Harmonization of the intracellular cytokine staining assay

Active immunotherapy for cancer is an accepted treatment modality aiming to reinforce the T-cell response to cancer. T-cell reactivity is measured by various assays and used to guide the clinical development of immunotherapeutics. However, data obtained across different institutions may vary substantially making comparative conclusions difficult. The Cancer Immunotherapy Immunoguiding Program organizes proficiency panels to identify key parameters influencing the outcome of commonly used T-cell assays followed by harmonization. Our successes with IFNγ-ELISPOT and peptide HLA multimer analysis have led to the current study on intracellular cytokine staining (ICS). We report the results of three successive panels evaluating this assay. At the beginning, 3 out of 9 participants (33 %) were able to detect >6 out of 8 known virus-specific T-cell responses in peripheral blood of healthy individuals. This increased to 50 % of the laboratories in the second phase. The reported percentages of cytokine-producing T cells by the different laboratories were highly variable with coefficients of variation well over 60 %. Variability could partially be explained by protocol-related differences in background cytokine production leading to sub-optimal signal-to-noise ratios. The large number of protocol variables prohibited identification of prime guidelines to harmonize the assays. In addition, the gating strategy used to identify reactive T cells had a major impact on assay outcome. Subsequent harmonization of the gating strategy considerably reduced the variability within the group of participants. In conclusion, we propose that first basic guidelines should be applied for gating in ICS experiments before harmonizing assay protocol variables

Impaired lymph node stromal cell function during the earliest phases of rheumatoid arthritis.

BACKGROUND: Systemic autoimmunity can be present years before clinical onset of rheumatoid arthritis (RA). Adaptive immunity is initiated in lymphoid tissue where lymph node stromal cells (LNSCs) regulate immune responses through their intimate connection with leucocytes. We postulate that malfunctioning of LNSCs creates a microenvironment in which normal immune responses are not properly controlled, possibly leading to autoimmune disease. In this study we established an experimental model for studying the functional capacities of human LNSCs during RA development. METHODS: Twenty-four patients with RA, 23 individuals positive for autoantibodies but without clinical disease (RA risk group) and 14 seronegative healthy control subjects underwent ultrasound-guided inguinal lymph node (LN) biopsy. Human LNSCs were isolated and expanded in vitro for functional analyses. In analogous co-cultures consisting of LNSCs and peripheral blood mononuclear cells, αCD3/αCD28-induced T-cell proliferation was measured using carboxyfluorescein diacetate succinimidyl ester dilution. RESULTS: Fibroblast-like cells expanded from the LN biopsy comprised of fibroblastic reticular cells (gp38+CD31-) and double-negative (gp38-CD31-) cells. Cultured LNSCs stably expressed characteristic adhesion molecules and cytokines. Basal expression of C-X-C motif chemokine ligand 12 (CXCL12) was lower in LNSCs from RA risk individuals than in those from healthy control subjects. Key LN chemokines C-C motif chemokine ligand (CCL19), CCL21 and CXCL13 were induced in LNSCs upon stimulation with tumour necrosis factor-α and lymphotoxin α1β2, but to a lesser extent in LNSCs from patients with RA. The effect of human LNSCs on T-cell proliferation was ratio-dependent and altered in RA LNSCs. CONCLUSIONS: Overall, we developed an experimental model to facilitate research on the role of LNSCs during the earliest phases of RA. Using this innovative model, we show, for the first time to our knowledge, that the LN stromal environment is changed during the earliest phases of RA, probably contributing to deregulated immune responses early in disease pathogenesis

Screening for developmental dysplasia of the hip in primary care : implementation by simulation

Developmental Dysplasia of the hip (DDH) is a disorder which occurs at an early age. Early discovery and treatment of DDH can reduce the chance on joint deviation in the future. Screening on DDH is done at a young age in the Netherlands. Current screening in the Netherlands exists from doing physical hip examination in combination with risk factor assessment. In the Netherlands this screening is organized by youth health care and takes place in infant health care centers (IHC). However, earlier research has shown that current screening on DDH is not valid. A high proportion of the referred children are unnecessary referred (86%). For this reason in the Netherlands, but also in other countries, the replacement of current screening by ultrasound screening is reviewed using method of R. Graf. In 2007, an implementation study has started in the Netherlands in which ultrasound screening is implemented in routine care of IHCs at the age of three months. This thesis describes the (cost-) effectiveness results of the implementation study. In total 15 IHCs participated in two areas, five in an urban area and ten in a rural area. In order to obtain a representative sample, the rural area organizations were located in different villages. The centers in the urban area were located in different social areas such as a high income inner city area, a low income inner city area and three relatively new suburban areas with a mixed population. Parents of 5266 children were asked to participate with their three month old child in this study. In total, 4080 children were screened using ultrasound to detect DDH at the age of three months. The US screening was performed by nurses and physicians working in the preventive IHC centers and by radiographic technicians. All screeners were theoretically trained in the screening method, according to Graf, by a pediatric radiologist and a pediatric orthopedic surgeon in three days. The results showed that there were no more missed cases compared to current screening (0.5%). Also, overall fewer children were referred compared to current screening (12% compared to 19 %) and also fewer children were incorrectly referred (37% compared to 86 %). Between the two regions the most important differences were participation rate (in the urban area 65% and 90% in the rural area), referral rate ( 7% in the urban area and 16% in the rural area) and screen detected cases (5% in the urban area and 10% in the rural area). The introduction of national quality control institute can help to introduce the screening in a safe way in routine practice through out the Netherlands

A tutorial on discrete-event simulation for health policy design and decision making: Optimizing pediatric ultrasound screening for hip dysplasia as an illustration

Background: It is increasingly recognized that healthcare is a complex system with limited resources and many interacting sources of both positive and negative feedback. Discrete-event simulation (DES) is a tool that readily accommodates questions of capacity planning, throughput management and interacting resources. As a result the use of DES in informing healthcare decision making is increasing. However, understanding when and how to build a DES model and use it for policy making is not yet a common knowledge. Methods: The steps in building a DES model will be demonstrated using a real-world example, i.e., pediatric ultrasound screening for hip dysplasia. The main components of a DES model such as entities, resources and queues will be introduced and we will examine questions such as referral schedule, number of ultrasound machines and type of screeners and how these entities interact. Finally a review of the statistical techniques appropriate to DES will be provided. Conclusion: Discrete-event simulation is a valuable tool in the policymakers armentarium. It can be used effectively to analyze and understand complex healthcare systems and policy problems such as population screening. (C) 2009 Elsevier Ireland Ltd. All rights reserved