Practical Tips on Sample Handling for Hematology, Chemistry, and Cytology Testing for Equine Patients:: Getting More Bang for your Buck.

Clinical pathology results are only as good as the quality of samples and accompanying information submitted to the diagnostic laboratory. The frustration of nondiagnostic or equivocal test results can often be avoided by taking the time to follow sample handling and submission guidelines. This article discusses preanalytical errors that commonly affect the accuracy of hematology, chemistry, and cytology testing, and offers practical tips for preventing these errors and maximizing diagnostic yield.

Sustainable Development of Pathology in Sub-Saharan Africa: An Example From Ghana.

CONTEXT: - Pathology services are poorly developed in Sub-Saharan Africa. Komfo Anokye Teaching Hospital in Kumasi, Ghana, asked for help from the pathology department of the University Hospital of North Norway, Tromsø. OBJECTIVE: - To reestablish surgical pathology and cytology in an African pathology department in which these functions had ceased completely, and to develop the department into a self-supporting unit of good international standard and with the capacity to train new pathologists. DESIGN: - Medical technologists from Kumasi were trained in histotechnology in Norway, they were returned to Kumasi, and they produced histologic slides that were temporarily sent to Norway for diagnosis. Two Ghanaian doctors received pathology training for 4 years in Norway. Mutual visits by pathologists and technologists from the 2 hospitals were arranged for the introduction of immunohistochemistry and cytology. Pathologists from Norway visited Kumasi for 1 month each year during 2007-2010. Microscopes and immunohistochemistry equipment were provided from Norway. Other laboratory equipment and a new building were provided by the Ghanaian hospital. RESULTS: - The Ghanaian hospital had a surgical pathology service from the first project year. At 11 years after the start of the project, the services included autopsy, surgical pathology, cytopathology, frozen sections, and limited use of immunohistochemistry, and the department had 10 residents at different levels of training. CONCLUSIONS: - A Ghanaian pathology department that performed autopsies only was developed into a self-supported department with surgical pathology, cytology, immunohistochemistry, and frozen section service, with an active residency program and the capacity for further development that is independent from assistance abroad.

Cost Effectiveness of Screening Patients With Gastroesophageal Reflux Disease for Barrett's Esophagus With a Minimally Invasive Cell Sampling Device.

BACKGROUND & AIMS: It is important to identify patients with Barrett's esophagus (BE), the precursor to esophageal adenocarcinoma (EAC). Patients with BE usually are identified by endoscopy, which is expensive. The Cytosponge, which collects tissue from the esophagus noninvasively, could be a cost-effective tool for screening individuals with gastroesophageal reflux disease (GERD) who are at increased risk for BE. We developed a model to analyze the cost effectiveness of using the Cytosponge in first-line screening of patients with GERD for BE with endoscopic confirmation, compared with endoscopy screening only. METHODS: We incorporated data from a large clinical trial of Cytosponge performance into 2 validated microsimulation models of EAC progression (the esophageal adenocarcinoma model from Massachusetts General Hospital and the microsimulation screening analysis model from Erasmus University Medical Center). The models were calibrated for US Surveillance, Epidemiology and End Results data on EAC incidence and mortality. In each model, we simulated the effect of a 1-time screen for BE in male patients with GERD, 60 years of age, using endoscopy alone or Cytosponge collection of tissue, and analysis for the level of trefoil factor 3 with endoscopic confirmation of positive results. For each strategy we recorded the number of cases of EAC that developed, the number of EAC cases detected with screening by Cytosponge only or by subsequent targeted surveillance, and the number of endoscopies needed. In addition, we recorded the cumulative costs (including indirect costs) incurred and quality-adjusted years of life lived within each strategy, discounted at a rate of 3% per year, and computed incremental cost-effectiveness ratios (ICERs) among the 3 strategies. RESULTS: According to the models, screening patients with GERD by Cytosponge with follow-up confirmation of positive results by endoscopy would reduce the cost of screening by 27% to 29% compared with screening by endoscopy, but led to 1.8 to 5.5 (per 1000 patients) fewer quality-adjusted life years. The ICERs for Cytosponge screening compared with no screening ranged from $26,358 to $33,307. For screening patients by endoscopy compared with Cytosponge the ICERs ranged from $107,583 to $330,361. These results were sensitive to Cytosponge cost within a plausible range of values. CONCLUSIONS: In a comparative modeling analysis of screening strategies for BE in patients with GERD, we found Cytosponge screening with endoscopic confirmation to be a cost-effective strategy. The greatest benefit was achieved by endoscopic screening, but with an unfavorable cost margin.

Cost-effectiveness of increasing cervical cancer screening coverage in the Middle East: An example from Lebanon.

BACKGROUND: Most cervical cancer (CC) cases in Lebanon are detected at later stages and associated with high mortality. There is no national organized CC screening program so screening is opportunistic and limited to women who can pay out-of-pocket. Therefore, a small percentage of women receive repeated screenings while most are under-or never screened. We evaluated the cost-effectiveness of increasing screening coverage and extending intervals. METHODS: We used an individual-based Monte Carlo model simulating HPV and CC natural history and screening. We calibrated the model to epidemiological data from Lebanon, including CC incidence and HPV type distribution. We evaluated cytology and HPV DNA screening for women aged 25-65years, varying coverage from 20 to 70% and frequency from 1 to 5years. RESULTS: At 20% coverage, annual cytologic screening reduced lifetime CC risk by 14% and had an incremental cost-effectiveness ratio of I$80,670/year of life saved (YLS), far exceeding Lebanon's gross domestic product (GDP) per capita (I$17,460), a commonly cited cost-effectiveness threshold. By comparison, increasing cytologic screening coverage to 50% and extending screening intervals to 3 and 5years provided greater CC reduction (26.1% and 21.4, respectively) at lower costs compared to 20% coverage with annual screening. Screening every 5years with HPV DNA testing at 50% coverage provided greater CC reductions than cytology at the same frequency (23.4%) and was cost-effective assuming a cost of I$18 per HPV test administered (I$12,210/YLS); HPV DNA testing every 4years at 50% coverage was also cost-effective at the same cost per test (I$16,340). Increasing coverage of annual cytology was not found to be cost-effective. CONCLUSION: Current practice of repeated cytology in a small percentage of women is inefficient. Increasing coverage to 50% with extended screening intervals provides greater health benefits at a reasonable cost and can more equitably distribute health gains. Novel HPV DNA strategies offer greater CC reductions and may be more cost-effective than cytology.

Cost-Effectiveness of Primary HPV Testing, Cytology and Co-testing as Cervical Cancer Screening for Women Above Age 30 Years.

BACKGROUND: Cervical cancer screening guidelines for women aged ≥30 years allow for co-testing or primary cytology testing. Our objective was to determine the test characteristics and costs associated with Cytology, HPV and Co-testing screening strategies. MAIN METHODS: Retrospective cohort study of women undergoing cervical cancer screening with both cytology and HPV (Hybrid Capture 2) testing from 2004 to 2010 in an integrated health system. The electronic health record was used to identify women aged ≥30 years who had co-testing. Unsatisfactory or unavailable test results and incorrectly ordered tests were excluded. The main outcome was biopsy-proven cervical intraepithelial neoplasia grade 3 or higher (CIN3+). KEY RESULTS: The final cohort consisted of 99,549 women. Subjects were mostly white (78.4 %), married (70.7 %), never smokers (61.3 %) and with private insurance (86.1 %). Overall, 5121 (5.1 %) tested positive for HPV and 6115 (6.1 %) had cytology ≥ ASCUS; 1681 had both and underwent colposcopy and 310 (0.3 %) had CIN3+. Sensitivity for CIN3+ was 91.9 % for Primary Cytology, 99.4 % for Co-testing, and 94.8 % for Primary HPV; specificity was 97.3 % for Co-testing and Primary Cytology and 97.9 % for Primary HPV. Over a 3-year screening interval, Primary HPV detected more cases of CIN3+ and was less expensive than Primary Cytology. Co-testing detected 14 more cases of CIN3+ than Primary HPV, but required an additional 100,277 cytology tests and 566 colposcopies at an added cost of $2.38 million, or $170,096 per additional case detected. CONCLUSIONS: Primary HPV was more effective and less expensive than Primary Cytology. Primary HPV screening appears to represent a cost-effective alternative to Co-testing.

Evaluation of cost effective diagnostic tools in characterisation of Acute Leukemia in Southern India.

The incidence of Acute Leukemia (AL) subtypes varies according to geographical distribution and more predominant in developing countries. The aim here was to evaluate the usefulness of cost effective diagnostic tools in characterization of Acute Lymphoblastic Leukemia (ALL) in resource poor population. One hundred and two AL cases were diagnosed. For diagnosis, cytochemical analysis and immunohistochemistry were performed. Among the children < 12 years, ALL was 64.3% while AML accounted for 30%. In patients > 12 years, ALL was 59.4% and AML was 31.3%. The B-ALL occurred most frequently than T-ALL in both the age groups while based on immunophenotyping in AML, CD13 was the most commonly expressed antigen. Hence, cost effective diagnostic tools namely the immunophenotyping and cytochemistry are useful and improve accuracy and rapidly risk-stratify patients that were diagnosed with acute leukemia.

Cost-Effectiveness of High-Risk Human Papillomavirus Testing With Messenger RNA Versus DNA Under United States Guidelines for Cervical Cancer Screening.

OBJECTIVES: To compare the cost-effectiveness of high-risk human papillomavirus (hrHPV) testing using a hrHPV DNA and a hrHPV messenger RNA (mRNA) assay under current US cervical cancer screening guidelines. METHODS: We constructed a Markov model for stochastic cost-effectiveness analysis using published data. We compared screening efficiency using DNA and mRNA testing for the following: (1) cotesting with cytology in women 30 to 65 years, and (2) triage of women with mild cervical cytological abnormalities (atypical squamous cells of undetermined significance [ASC-US]) in the United States. Screening end point is histologically confirmed high-grade lesions (cervical intraepithelial neoplasia grade 2, 3, or invasive cancer). Sensitivity and specificity estimates of DNA and mRNA testing to detect cervical intraepithelial neoplasia grade 2, 3, or invasive cancer were obtained from 2 published trials: the US Clinical Evaluation of APTIMA mRNA (CLEAR) study for ASC-US triage and the French APTIMA Screening Evaluation (FASE) study for cotesting. Costs of DNA and mRNA testing were assumed identical. Costs of screening, diagnosis, and treatment of cervical neoplasia and cancer were from previously published estimates, adjusted to 2012 US dollars. Inputs were modeled as distributions for Monte Carlo probabilistic sensitivity analysis. Model outcomes were costs per life-year saved for each strategy, discounted at 3% annually. RESULTS: For both cotesting and ASC-US triage, mRNA testing cost less than DNA testing, whereas life expectancies were widely overlapping. There was a 100% probability that DNA testing was not cost-effective at $100,000/life-year saved threshold for ASC-US triage and a 55% probability that DNA testing was not cost-effective at the same threshold for cotesting. CONCLUSIONS: Based on the available evidence, mRNA testing for cotesting or ASC-US triage is likely to be more efficient than DNA testing under current US cervical cancer screening guidelines.

Economic evaluation of DNA ploidy analysis vs liquid-based cytology for cervical screening.

BACKGROUND: DNA ploidy analysis involves automated quantification of chromosomal aneuploidy, a potential marker of progression toward cervical carcinoma. We evaluated the cost-effectiveness of this method for cervical screening, comparing five ploidy strategies (using different numbers of aneuploid cells as cut points) with liquid-based Papanicolaou smear and no screening. METHODS: A state-transition Markov model simulated the natural history of HPV infection and possible progression into cervical neoplasia in a cohort of 12-year-old females. The analysis evaluated cost in 2012 US$ and effectiveness in quality-adjusted life-years (QALYs) from a health-system perspective throughout a lifetime horizon in the US setting. We calculated incremental cost-effectiveness ratios (ICERs) to determine the best strategy. The robustness of optimal choices was examined in deterministic and probabilistic sensitivity analyses. RESULTS: In the base-case analysis, the ploidy 4 cell strategy was cost-effective, yielding an increase of 0.032 QALY and an ICER of $18 264/QALY compared to no screening. For most scenarios in the deterministic sensitivity analysis, the ploidy 4 cell strategy was the only cost-effective strategy. Cost-effectiveness acceptability curves showed that this strategy was more likely to be cost-effective than the Papanicolaou smear. CONCLUSION: Compared to the liquid-based Papanicolaou smear, screening with a DNA ploidy strategy appeared less costly and comparably effective.

Apoptotic primary normal human dermal fibroblasts for in vitro models of fibrosis.

Recent studies show that apoptosis affects surrounding tissue, playing a role in diseases such as fibrosis, a significant global disease burden. Elucidating the mechanisms by which the different apoptotic cells present during fibrotic wound healing affect their environment would enable development of new therapies. We describe here a simple, rapid, and cost-effective method for inducing apoptosis of primary normal human dermal fibroblasts without affecting the overall cell viability of the population. Such population could be used for in vitro models of fibrotic wound healing in co-culture with other cells involved in this process to study events such as apoptosis-induced proliferation.

A novel feeder-free culture system for expansion of mouse spermatogonial stem cells.

Spermatogonial stem cells (SSCs, also called germline stem cells) are self-renewing unipotent stem cells that produce differentiating germ cells in the testis. SSCs can be isolated from the testis and cultured in vitro for long-term periods in the presence of feeder cells (often mouse embryonic fibroblasts). However, the maintenance of SSC feeder culture systems is tedious because preparation of feeder cells is needed at each subculture. In this study, we developed a Matrigel-based feeder-free culture system for long-term propagation of SSCs. Although several in vitro SSC culture systems without feeder cells have been previously described, our Matrigel-based feeder-free culture system is time- and cost- effective, and preserves self-renewability of SSCs. In addition, the growth rate of SSCs cultured using our newly developed system is equivalent to that in feeder cultures. We confirmed that the feeder-free cultured SSCs expressed germ cell markers both at the mRNA and protein levels. Furthermore, the functionality of feeder-free cultured SSCs was confirmed by their transplantation into germ cell-depleted mice. These results suggest that our newly developed feeder-free culture system provides a simple approach to maintaining SSCs in vitro and studying the basic biology of SSCs, including determination of their fate.

Cost-effectiveness analysis of 2 surveillance options for cervical intraepithelial neoplasia 1.

OBJECTIVE: We aim to determine the difference in cost between 2 accepted surveillance strategies for women diagnosed with cervical intraepithelial neoplasia 1 (CIN 1): repeat cytology at 6 and 12 months versus human papillomavirus (HPV) DNA testing at 12 months. MATERIALS AND METHODS: Extracting data from the literature regarding the natural history of HPV infection and CIN 1, we estimated regression, persistence, and progression rates during a 2-year interval. Costs were based on 2011 Medicaid reimbursements for cytology, biopsy interpretation, HPV testing, and the associated office visit or procedure fee. We constructed a decision tree model to estimate the potential cost benefits of using HPV testing, and sensitivity analyses were performed. Treatment costs for high-grade disease were not included because of equal occurrence in both groups. RESULTS: In a hypothetical cohort of 100 women with CIN 1 (assumed compliant with 2 y of follow-up), the total cost for cytology-based follow-up was $89,969, whereas the total cost for HPV-based follow-up was $37,357. This indicates an average cost savings of $526 per patient in favor of HPV testing. If we then consider the 234,603 incident cases of CIN 1 in the United Sates per year, preferential use of HPV-based follow-up would save $123,429,305. CONCLUSIONS: Although both cytology and HPV testing are sound methods for surveillance of CIN 1, it is more cost-effective to use HPV testing.

Design and use of multiplexed chemostat arrays.

Chemostats are continuous culture systems in which cells are grown in a tightly controlled, chemically constant environment where culture density is constrained by limiting specific nutrients.(1,2) Data from chemostats are highly reproducible for the measurement of quantitative phenotypes as they provide a constant growth rate and environment at steady state. For these reasons, chemostats have become useful tools for fine-scale characterization of physiology through analysis of gene expression(3-6) and other characteristics of cultures at steady-state equilibrium.(7) Long-term experiments in chemostats can highlight specific trajectories that microbial populations adopt during adaptive evolution in a controlled environment. In fact, chemostats have been used for experimental evolution since their invention.(8) A common result in evolution experiments is for each biological replicate to acquire a unique repertoire of mutations.(9-13) This diversity suggests that there is much left to be discovered by performing evolution experiments with far greater throughput. We present here the design and operation of a relatively simple, low cost array of miniature chemostats-or ministats-and validate their use in determination of physiology and in evolution experiments with yeast. This approach entails growth of tens of chemostats run off a single multiplexed peristaltic pump. The cultures are maintained at a 20 ml working volume, which is practical for a variety of applications. It is our hope that increasing throughput, decreasing expense, and providing detailed building and operation instructions may also motivate research and industrial application of this design as a general platform for functionally characterizing large numbers of strains, species, and growth parameters, as well as genetic or drug libraries.

Expenditure and resource utilisation for cervical screening in Australia.

BACKGROUND: The National Cervical Screening Program in Australia currently recommends that women aged 18-69 years are screened with conventional cytology every 2 years. Publicly funded HPV vaccination was introduced in 2007, and partly as a consequence, a renewal of the screening program that includes a review of screening recommendations has recently been announced. This study aimed to provide a baseline for such a review by quantifying screening program resource utilisation and costs in 2010. METHODS: A detailed model of current cervical screening practice in Australia was constructed and we used data from the Victorian Cervical Cytology Registry to model age-specific compliance with screening and follow-up. We applied model-derived rate estimates to the 2010 Australian female population to calculate costs and numbers of colposcopies, biopsies, treatments for precancer and cervical cancers in that year, assuming that the numbers of these procedures were not yet substantially impacted by vaccination. RESULTS: The total cost of the screening program in 2010 (excluding administrative program overheads) was estimated to be A$194.8M. We estimated that a total of 1.7 million primary screening smears costing $96.7M were conducted, a further 188,900 smears costing $10.9M were conducted to follow-up low grade abnormalities, 70,900 colposcopy and 34,100 histological evaluations together costing $21.2M were conducted, and about 18,900 treatments for precancerous lesions were performed (including retreatments), associated with a cost of $45.5M for treatment and post-treatment follow-up. We also estimated that $20.5M was spent on work-up and treatment for approximately 761 women diagnosed with invasive cervical cancer. Overall, an estimated $23 was spent in 2010 for each adult woman in Australia on cervical screening program-related activities. CONCLUSIONS: Approximately half of the total cost of the screening program is spent on delivery of primary screening tests; but the introduction of HPV vaccination, new technologies, increasing the interval and changing the age range of screening is expected to have a substantial impact on this expenditure, as well as having some impact on follow-up and management costs. These estimates provide a benchmark for future assessment of the impact of changes to screening program recommendations to the costs of cervical screening in Australia.

[Health technology assessment report. Use of liquid-based cytology for cervical cancer precursors screening]. / Health Technology assessment Report. Uso della citologia in fase liquida nello screening dei precursori del cancro del collo uterino.

OBJECTIVE OF THE PROJECT: Purpose of this Report is to evaluate the impact of the introduction of liquid-based cytology (LBC) in cervical cancer screening in terms of efficacy, undesired effects, costs and implications for organisation. EFFICACY AND UNDESIRED EFFECTS: LBC WITH MANUAL INTERPRETATION: The estimates of cross-sectional accuracy for high-grade intraepithelial neoplasia (CIN2 or more severe and CIN3 or more severe) obtained by a systematic review and meta-analysis published in 2008 were used. This review considered only studies in which all women underwent colposcopy or randomised controlled trials (RCTs) with complete verification of test positives. A systematic search of RCTs published thereafter was performed. Three RCTs were identified. One of these studies was conducted in 6 Italian regions and was of large size (45,174 women randomised); a second one was conducted in another Italian region (Abruzzo) and was of smaller size (8,654 women randomised); a third RCT was conducted in the Netherlands and was of large size (89,784 women randomised). No longitudinal study was available. There is currently no clear evidence that LBC increases the sensitivity of cytology and even less that its introduction increases the efficacy of cervical screening in preventing invasive cancers. The Italian randomised study NTCC showed a decrease in specificity, which was not observed in the other two RCTs available. In addition, the 2008 meta-analysis observed a reduction - even if minimal - in specificity just at the ASC-US cytological cut-off, but also a remarkable heterogeneity between studies. These results suggest that the effect of LBC on specificity is variable and plausibly related to the local style of cytology interpretation. There is evidence that LBC reduces the proportion of unsatisfactory slides, although the size of this effect varies remarkably. LBC WITH COMPUTER-ASSISTED INTERPRETATION: An Australian study, based on double testing, showed a statistically significant increase of the sensitivity for CIN2 or more of LBC with computer-assisted interpretation vs. conventional cytology with manual interpretation. However, an English RCT estimated that LBC with computer-assisted interpretation has a lower sensitivity than LBC with manual interpretation. COST AND ECONOMIC EVALUATION: In the current Italian situation the use of liquid-based cytology for primary screening is estimated to increase the costs of cytological screening. Liquid-based cytology needs shorter time for interpretation than conventional cytology. However, in the Italian situation, savings obtained from this time reduction and from the decreased number of repeats due to unsatisfactory slides are not currently sufficient to compensate the cost increase due to the prices currently applied by producers and to a possible greater number of colposcopies caused by LBC. In any case, at current prices, cost is estimated to increase even when assuming a referral rate to colposcopy with LBC similar or slightly lower than that with conventional cytology. For the costs of computer-assisted interpretation of liquid-based cytology, readers are referred to the relative HTA report (Epidemiol Prev 2012;36(5) Suppl 3:e1-43). ORGANISATIONAL AND ETHICAL ASPECTS: Ethical, legal and communication problems are judged to remain unchanged when compared to screening with conventional cytology. After having used the test for some time, interpreters prefer liquid-based to conventional cytology. Reduced time for interpretation makes the adoption of LBC a possible approach to deal with shortenings of cytology interpreters which is happening in Italy. However, alternative solutions, such as computer-assisted interpretation of cytology and the use of HPV as primary screening test, should be considered. Liquid-based cytology allows performing molecular tests, in particular the HPV test. This property allows triaging women with borderline or mild cytology by "reflex" molecular or immunocytochemical tests with no need to recall them. LBC sampling can be used also if HPV is applied as the primary screening test, allowing "reflex" triaging of HPV positive women by cytology with no need to recall them nor to take two samples, one for HPV testing and one for conventional cytology. This represents a remarkable advantage in terms of organization. However, costs are high because only 5-7% of women screened with this approach need interpretation of cytology. In addition, HPV testing with the Hybrid Capture assay on material preserved in LBC transport media needs a preliminary conversion phase, which limits the use of LBC for triaging HPV positive women. It is advisable that in the near future industry develops sampling/transport systems that allow performing both the HPV test and cytology or other validated triage tests without additional manipulations and at sustainable costs.

Cost and logistics of alternative roll-out options for implementing human papillomavirus testing as a triage in cervical screening: results of the sentinel sites study.

BACKGROUND: Previous studies have indicated that human papillomavirus (HPV) testing as a triage for managing equivocal cytology is cost-effective. The aim of this study was to assess the costs of alternative roll-out options. METHODS: Detailed cost estimates were collected from six laboratories where HPV triage had been implemented. Costs were assessed for the two different service delivery models that were implemented; a 'hub and spoke model' of central HPV testing in a microbiology laboratory with separate cytology laboratories, and an 'integrated model' where HPV testing was conducted within the cytology laboratory. RESULTS: Comparison of alternative delivery models indicated that setting up HPV processing within existing cytology laboratory, i.e., an 'integrated cytology/HPV laboratory' generated savings in staff time amounting to between £2.54 and 4.86 per sample processed. Running full HPV testing batches was also an important consideration. For full batches to be run on a twice weekly basis requires having no more than two laboratories per Strategic Health Authority. CONCLUSIONS: To be cost-efficient, and to meet turn-around times, HPV testing needs to be conducted at integrated cytology/HPV testing centres with sufficient throughput to run full batches of HPV tests.

Manual liquid based cytology in primary screening for cervical cancer--a cost effective preposition for scarce resource settings.

Conventional pap smear (CPS) examination has been the mainstay for early detection of cervical cancer. However, its widespread use has not been possible due to the inherent limitations, like presence of obscuring blood and inflammation, reducing its sensitivity considerably. Automated methods in use in developed countries may not be affordable in the developing countries due to paucity of resources. On the other hand, manual liquid based cytology (MLBC) is a technique that is cost effective and improves detection of precursor lesions and specimen adequacy. Therefore the aim of the study was to compare the utility of MLBC with that of CPS in cervical cancer screening. A prospective study of 100 cases through MLBC and CPS was conducted from October 2009 to July 2010, in a Medical College in India, by two independent pathologists and correlated with histopathology (22 cases). Morphological features as seen through MLBC and CPS were compared. Subsequently, all the cases were grouped based on cytological diagnosis according to two methods into 10 groups and a subjective comparison was made. In order to compare the validity of MLBC with CPS in case of major diagnoses, sensitivity and specificity of the two methods were estimated considering histological examination as the gold standard. Increased detection rate with MLBC was 150%. The concordance rate by LBC/histopathology v/s CPS/histopathology was also improved (86% vs 77%) The percentage agreement by the two methods was 68%. MLBC was more sensitive in diagnosis of LSIL and more specific in the diagnosis of inflammation. Thus, MLBC was found to be better than CPS in diagnosis of precursor lesions. It provided better morphology with increased detection of abnormalities and preservation of specimen for cell block and ancillary studies like immunocytochemistry and HPV detection. Therefore, it can be used as alternative strategy for cervical cancer prevention in limited resource settings.

An evaluation of the ability of leucocyte depletion filters to remove components of amniotic fluid.

Haemorrhage remains an important cause of maternal mortality worldwide. Cell salvage carries a theoretical risk of amniotic fluid embolus syndrome and is too expensive for use in many parts of the world. To explore cheaper options, we investigated whether a leucocyte depletion filter alone removes components of pure amniotic fluid. Amniotic fluid was collected from 10 women during elective caesarean section and passed through a LeukoGuard® RS filter. Pre- and post-filtration samples were compared in the laboratory. Lamellar bodies and fetal squames were almost completely removed (filtration efficacy 96.6% and 99.9%, respectively; p<0.0001 and <0.0004), and hair was completely removed (p=0.002). Filtration had no effect on concentrations of α-fetoprotein, tissue factor or endothelin-1, or on the presence of meconium or vernix. Additional work is required to evaluate whether cell salvage using filtration alone may be useful in maternal haemorrhage in the developing world.

Liquid-based cervical cytology using ThinPrep technology: weighing the pros and cons in a cost-effectiveness analysis.

PURPOSE: Cervical cancer screening with liquid-based cytology (LBC) has been developed as an alternative to the conventional Papanicolaou (CP) smear. Cost-effectiveness is one of the issues when evaluating LBC. Based on the results of a Dutch randomised controlled trial, we conducted cost-effectiveness threshold analyses to investigate under what circumstances manually screened ThinPrep LBC is cost-effective for screening. METHODS: The MISCAN-Cervix microsimulation model and data from the Dutch NETHCON trial (including 89,784 women) were used to estimate the costs and (quality-adjusted) life years ((QA)LYs) gained for EU screening schedules, varying cost-effectiveness threshold values. Screening strategies were primary cytological screening with LBC or CP, and triage with human papillomavirus (HPV) testing. RESULTS: Threshold analyses showed that screening with LBC as a primary test can be cost-effective if LBC is less than 3.2 more costly per test than CP, if the sensitivity of LBC is at least 3-5 % points higher than CP, if the quality of life for women in triage follow-up is only 0.39, or if the rate of inadequate CP smears is at least 16.2 %. CONCLUSIONS: Regarding test characteristics and costs of LBC and CP, only under certain conditions will a change from CP to manually screened ThinPrep LBC be cost-effective. If none of these conditions are met, implementation of manually screened ThinPrep LBC seems warranted only if there are advantages other than cost-effectiveness. Further research is needed to establish whether other LBC systems will be more favorable with regard to cost-effectiveness.