Unacceptable Variation Research Articles

The national clinical audit of falls and bone health: The clinical management of hip fracture patients

Background The standards of care for older people who present with a fractured neck of femur (#NOF) have been defined by previously published national guidelines. To assess compliance with these standards the Healthcare Commission commissioned the Clinical Effectiveness and Evaluation Unit (CEEU) for the Royal College of Physicians to deliver ‘The National Clinical Audit of Falls and Bone Health for Older People’. Methods The audit was developed by a multi-disciplinary team using available best evidence to set audit standards. All acute hospital trusts admitting orthopaedic trauma cases and all primary care trusts (PCTs) in England were recruited. Patients >65 years old presenting with a proven #NOF were included in the audit with a target of 20 cases per participating site. Results Data was entered for 3184 #NOF patients. 80% (2555/3184) were female with a median age of 83 years admitted from their own home (68% 2152/3184). Over 97% (3172/3184) presented to the A&E department on the same day as the fall (88% 2813/3184). The time in the A&E department was less than 2 h in only 20% (640/3133) of cases with 23% (716/3133) having a stay of >240 min. 35% (1080/3088) of #NOF patients were operated on within 24 h of admission. Causes of delay to theatre included awaiting medical review (59% 566/956) or organisational reasons (29% 278/956). 48% (1480/2998) of patients were sat out of bed within 24 h. Only 35% (1115/3184) of patients were cared for in an orthogeriatric setting. The median length of stay for the #NOF patients was 16 days with an interquartile range of 10–27 days. Conclusions There are currently unacceptable wide variations in the delivery of clinical care to older people presenting with a #NOF. Of concern were the long lengths of time in A&E for many patients and the low level of routine access to pre-operative medical assessment. It is hoped that the launch of joint initiatives between the British Orthopaedic Association and the British Geriatric Society aimed at delivering service improvements in this area should lead to improved outcomes.

Unacceptable variation in abdominal excision rates for rectal cancer

Unacceptable variation in abdominal excision rates for rectal cancer

Use of Bone Turnover Markers in the Real World: Are We There Yet?

Early identification of the patient at risk for osteoporosis is pivotal for the effective prevention and management of a condition that, if unrecognized, almost invariably deteriorates, leading to considerable complications such as fractures, chronic pain, immobility, social isolation, and death. Over the years, we have learned that, in addition to the well-known clinical risk factors of osteoporosis, accelerated bone turnover is associated with a higher risk of fracture, independent of age, sex, body weight, disability, and bone mass. Hence, the rate of bone turnover seems to determine aspects of bone strength that are distinct from, and are not captured by the measurement of bone mass, structure or geometry. The last 20 yr have seen considerable progress in the development and validation of serum and urine markers of bone turnover. If applied and interpreted correctly, these indices permit the specific measurement of bone formation or bone resorption without the need of going through the process of a bone biopsy. Today, there is little doubt that markers of bone turnover can be used to estimate fracture risk in both postmenopausal women and older men. However, the real domain for the use of bone turnover markers in clinical practice seems to lie in the monitoring of anti-osteoporotic therapy, treatment efficacy, and patient compliance. In contrast to changes in BMD, which occur slowly and may not be detectable before several years of treatment, biochemical markers of bone turnover change rapidly in response to therapeutic interventions. Based on these findings, and through the intense efforts of commercialization and automatization, ‘‘bone markers’’ are today considered useful tools that many would like to see applied in the diagnosis and management of metabolic bone disease, including osteoporosis. Thus far, however, the productive use of these markers has been confined mostly to research studies or commercial trials, which, as a rule, look at larger populations rather than the individual patient. As a matter fact, most current practice guidelines are very clear in not recommending the use of bone turnover markers in routine clinical practice. The reasons for the apprehensiveness of most independent experts and professional societies in regard to the widespread use of bone turnover markers are 3-fold: first, the variability of nearly all bone markers makes it difficult to apply the results derived from larger trials to individual patients; second, many countries lack pivotal quality control programs for bone turnover markers, including those offered by commercial laboratories—this deficit is further confounded by poor standardization of most assays; and third, the lack of valid reference ranges leaves many clinicians with uncertainties how to interpret a given result. It is in this context that the paper by Glover et al. in this issue of the Journal is of particular interest. Based on an international study of 637 premenopausal women, the investigators aimed to set-up reference intervals for two well-established markers of bone formation (bone alkaline phosphatase [ALP], N-terminal propeptide of type I procollagen [PINP]) and two markers of bone resorption (serum C-terminal telopeptide of type I collagen [S-CTX], urinary N-terminal telopeptide of type I collagen [UNTX]). Premenopausal volunteers eligible to participate were women between the age of 30 and 39 yr with a BMI between 18 and 29 kg/m and without medical conditions known to affect bone metabolism (although some were taking an oral contraceptive pill). All samples were obtained at roughly the same time of the year (in the northern summer) and time of day (i.e., between 8:00 a.m. and 10:00 a.m.) after an overnight fast. The study is strengthened by its relatively large sample size, its reasonably well-characterized study population, and a strict study protocol within the wider context of the HORIZON-PFT trial. Although the authors paid special attention to minimize variability in their study cohorts, serum levels of bone turnover markers (PINP, S-CTX) were found to be different between study centers in the United Kingdom, France, Belgium, and the United States. For instance, women in France showed significantly higher mean levels of S-CTX relative to those living in the United Kingdom and significantly higher mean levels of PINP than women living in Belgium and the United Kingdom. The regional differences observed in this study were in part explained by variations in BMI and lifestyle factors such as smoking habits, use of the oral contraceptive pill, exercise levels, and alcohol consumption. These findings again highlight the clinically important fact that bone marker levels are affected by a number of modifiable and nonmodifiable

Do European hospitals have quality and safety governance systems and structures in place?

Internal systems for quality and safety were assessed in 89 hospitals in six European states, by external teams using standardised criteria and procedures, as part of the Methods of Assessing...

Dynamic Response Analysis and Control of Slot Coating

A slot coating application is an attractive coating method for creating a uniform coating thickness over a substrate material. However, a variety of disturbances in operational conditions (e.g., pumping fluctuations, motor system cogging) may lead to unacceptable variations in the final coating thickness. The dynamic response characteristics of the final coating thickness resulting from such disturbances can be computed using a numerical analysis technique that employs a visco-capillary model. In addition, there are two different methods for controlling the thickness of the final coating. One passive control method changes die lip geometry, and the other active control method uses a flow feedback system coupled with a final coating thickness sensor. The passive technique can suppress final thickness variations by 20-30% in a limited number of cases, whereas the active technique substantially reduces thickness variations in every case where the disturbance frequency is less than 10 Hz.

The Effectiveness of Integrated Care Pathways for Adults and Children in Health Care Settings: A Systematic Review.

Background Integrated Care Pathways (ICPs) are management technologies which formalise multi-disciplinary team-working and enable professionals to examine and address how they articulate their respective roles, responsibilities and activities. They map out a patient’s journey and aim to have: ‘the right people, doing the right things, in the right order, at the right time, in the right place, with the right outcome’. Initially introduced into the health care context in the 1980s in the US, enthusiasm for ICPs now extends across the world. They have been promoted as a means to realise: evidence based practice, clinical governance, continuity of care, patient empowerment, efficiency gains, service re-engineering, role realignment and staff education. While ICPs are now being developed and implemented across international health care arena, evidence to support their use is equivocal and understanding of their ‘active ingredients’ is poor. Reviews of evidence of ICP effectiveness have focused on their use in specific patient populations. However, ICPs are ‘complex interventions’ and are increasingly being implemented for a variety of purposes in a range of organisational contexts. Identification of the circumstances in which ICPs are effective is the first step towards developing hypotheses about their active ingredients and the generative mechanisms by which they have their effects. This review was designed to address a slightly different set of questions to those that typify systematic reviews of ICP effectiveness. Rather than simply asking: ‘Are ICPs effective?’, our concern was to identify the circumstances in which ICPs are effective, for whom and in what contexts. In addition to identifying evidence of ICP effectiveness, the review therefore required attention to the contexts in which ICPs are utilised, the purposes to which they are put and the factors critical to their success. In framing the review in this way we are drawing on the insights afforded by Pawson and Tilley’s realistic evaluation methodology. The underlying rationale for this approach is that if we know and understand how different interventions produce varying effects in different circumstances, we are better able to decide what policies/services to implement in what conditions. Objectives To identify the purposes for which ICPs are effective, for whom and in what contexts; To identify the purposes for which ICPs are not effective, for whom and in what contexts; To produce recommendations on how ICPs should be used in the full range of health care settings. Inclusion Criteria Types of participants The review focused on adults and children that accessed health care settings in which ICPs are used. Types of intervention(s)/phenomena of interest For the purposes of the review, the ICP had to meet the defining characteristics set by the European Pathway Association (EPA): An explicit statement of the goals and key elements of care based on evidence, best practice and patient expectations; Facilitation of communication, coordination of roles, and sequencing of activities of the multidisciplinary care team, patients and their relatives; The documentation, monitoring, and evaluation of variances and outcomes; The identification of the appropriate resources. Here multidisciplinary is taken to refer to the involvement of two or more disciplines. Types of outcomes Outcome measures were determined by the purposes of the studies selected for review and the type of study participant. Specific clinical outcomes were determined by the group of patients for which the ICP was developed. Types of studies To address the aims of the review it was necessary to examine evidence of ICP effectiveness across the full spectrum of contexts in which they are in use. In order to keep the study to a manageable scale we limited its scope to randomised controlled trials (RCTs). All RCTs reported TRUNCATED AT 600 WORDS.

A caring profession?

The delivery of ‘High Quality Care for All’ (DH, 2008) has been a catalyst for some interesting reports commissioned by the Chief Nursing Officer (CNO) for England, Professor Dame Christine Beasley, from the National Nursing Research Unit (Kings College, London) to highlight the role of nursing in current and future health care delivery. ‘Nurses in Society: Starting the Debate’ (Maben and Griffiths, 2008) was prompted by a sense that nursing had lost its way and that there were unacceptable variations in the quality of care. The report reviews the many influences on nursing roles from sociological to educational and suggests a potential model for ‘the future registered nurse: practitioner, partner, leader’ (p15). It links well with a sister report also released in October ‘State of the Art Metrics: A Rapid Appraisal’ (Griffiths et al, 2008). This much-needed work on defining how to measure the nursing contribution to delivery and outcomes of care attempts to identify ways of incorporating more qualitative measures rather than the quantitative rates of infection, numbers of patients treated and the like.

Commentary: State Snapshots—A Picture of Unacceptable Variation: Are We Destined to Live With “Geography Is Destiny”?

Commentary: State Snapshots—A Picture of Unacceptable Variation: Are We Destined to Live With “Geography Is Destiny”?

How to estimate GFR in children

The reference method to determine glomerular filtration rate (GFR) in children is the inulin clearance. Similarly, Cr51-EDTA, iohexol and iothalamate can be used as exogenous GFR markers [1,2]. Exogenous markers are expensive and rather impractical. Creatinine is by far the most commonly used biochemical marker of renal function. The commonest principle for assaying creatinine is the Jaffe reaction [3]. Since Jaffe only observed a complexation between picric acid and creatinine in alkaline environment and never described an analytical method, variation amongst ‘Jaffe method’ recipes is broad [4]. The analytical bias of current creatinine methods (due to interference by pseudochromogens and calibration differences) is still disappointing: the compensated Jaffe method shows a small positive bias, whereas a major positive bias is observed for the dry chemistry and the uncompensated Jaffe methods [5]. Interlaboratory variation for creatinine is still unacceptably high; recent studies have reported median method group variation coefficients of 6.4% at a concentration of 80μmol/L [6]. Such variation leads to an unacceptable variation in the estimation of kidney function in young children and infants. Equations to estimate GFR require knowledge of the calibration of the serum creatinine assay [7].

Unacceptable variation in abdominoperineal excision rates for rectal cancer: time to intervene?

Objective:To determine the variation in the rates of use of abdominoperineal excision (APE) by cancer network, hospital trust and surgeon across England between 1998 and 2004 and determine if any...

The mating behavior and reproduction performance in a multi-sire mating system for pigs

An important aim of organic animal production is to allow natural animal behaviour. Regarding reproduction techniques, artificial insemination is permitted but natural mating is preferred. The outdoor multi-sire system, where the sows are placed in large paddocks with a group of boars, is one example of a service system, which complies well with the organic ideals of facilitating natural animal behavior. However, very little knowledge is available about such system. Seven groups of in total of 47 sows and 31 boars were observed to study the mating behavior in an outdoor multi-sire mating system and the subsequent reproduction results. The time of start of courtship, behavior and the cause of disruption if the courtship was terminated, were recorded each time a boar courted a sow. All aggressive interactions between the boars were also recorded to estimate the boar ranking order. The observations revealed numerous poor quality matings, a huge variation in the number of times sows are mated, and overworked boars. Only 35% of all copulations lasted 2min or more and 63% of all copulations were disrupted, mainly by competitor boars. The higher social status of the boar, the more copulations did it disrupt (p<0.05). The outcome was an unacceptable variation in reproduction results. Only 71% of all estrus sows conceived, corresponding to a pregnancy rate of 77% of all mated sows. A large inter-group variation in reproduction performance was observed, indicating scope for improvements. In some groups all sows showed estrus and all sows conceived. Recommendations for improvement of the system are proposed.

Response of slot coating flows to periodic disturbances

Slot coating is a common method in the manufacture of a wide variety of products. It belongs to a class of coating method known as premetered coating: in a steady-state operation, the thickness of the coated liquid layer is set by the flow rate fed to the die and the speed of the substrate moving past, and is independent of other process variables. Thus premetered methods are ideal for high precision coating. However, even the best designed slot coating operations are subjected to small oscillations on the process conditions, such as flow rate, vacuum pressure and gap fluctuations. These oscillation may lead to unacceptable variation on the thickness of the deposited liquid layer. The effect of process condition disturbances on the coated layer has to be minimized to assure a wet thickness as uniform as possible. The effect of an imposed periodic perturbation on the liquid flow rate or on the gap clearance in the coated layer thickness is explored in this work by computer-aided analysis. The amplitude of the thickness variation is determined at different process conditions and die configurations by solving the transient, two-dimensional, viscous free surface liquid flow in the coating bead. The system of equations, with appropriate boundary conditions, was solved by the Galerkin/finite element method, and an implicit time integration. The results show the response as a function of the imposed perturbation frequency and of the die geometry. They indicate that the die geometry may be optimized in order to minimize the film thickness oscillation of a slot coating operation.

Trueness verification of actual creatinine assays in the European market demonstrates a disappointing variability that needs substantial improvement. An international study in the framework of the EC4 creatinine standardization working group

The European In Vitro Diagnostics (IVD) directive requires traceability to reference methods and materials of analytes. It is a task of the profession to verify the trueness of results and IVD compatibility. The results of a trueness verification study by the European Communities Confederation of Clinical Chemistry (EC4) working group on creatinine standardization are described, in which 189 European laboratories analyzed serum creatinine in a commutable serum-based material, using analytical systems from seven companies. Values were targeted using isotope dilution gas chromatography/mass spectrometry. Results were tested on their compliance to a set of three criteria: trueness, i.e., no significant bias relative to the target value, between-laboratory variation and within-laboratory variation relative to the maximum allowable error. For the lower and intermediate level, values differed significantly from the target value in the Jaffe and the dry chemistry methods. At the high level, dry chemistry yielded higher results. Between-laboratory coefficients of variation ranged from 4.37% to 8.74%. Total error budget was mainly consumed by the bias. Non-compensated Jaffe methods largely exceeded the total error budget. Best results were obtained for the enzymatic method. The dry chemistry method consumed a large part of its error budget due to calibration bias. Despite the European IVD directive and the growing needs for creatinine standardization, an unacceptable inter-laboratory variation was observed, which was mainly due to calibration differences. The calibration variation has major clinical consequences, in particular in pediatrics, where reference ranges for serum and plasma creatinine are low, and in the estimation of glomerular filtration rate.

NICE: Managing conflict

Some of the strengths of NICE (the National Institute for Health and Clinical Excellence) are that it ‘sees guidelines as guidelines, not as rules set in stone’, adopts ‘flexible approaches’, and does not ‘expect its pronouncements to be accepted without questioning’ (JRSM 2007;100:442-3).1 It thrives on argument, as the recent papers in the October 2007 issue of the JRSM demonstrate, and grows stronger through debate and controversy. This is hardly surprising, given that it has the task of promoting cost-effective use of resources whilst also encouraging innovation, improving quality and reducing variation in practice, in response to the need to deal with clinical and budgetary uncertainties about therapies (JRSM 2007;100:453-60).2 It stands, therefore, at the controversial intersection of quality, innovation, access and cost, with a remit to operate in a transparent and inclusive way, using cost effectiveness to inform decisions about treatments, without considering their affordability.3 As an organization it is designed to manage conflicts of opinion, not avoid them, and it is becoming increasingly capable of doing so. NICE was established to correct inequalities and inefficiencies in health care, including unacceptable variations in the uptake of technologies of proven value, failure to provide patients with optimum care for the treatment of common diseases and the too-ready adoption of therapies with no proven clinical benefit.4 It is, therefore, an openly political body. NICE operates a form of deliberative democracy which engages clinicians, researchers, industry, economists and public organizations in an iterative process of decision making. This deliberative democracy has proved beneficial to clinicians, patients and the pharmaceutical industry. For example, the decisions made by NICE about neuropsychiatric agents like the atypical antipsychotics and the cholinesterase inhibitors have lifted restrictions on their funding and facilitated their wider use. Likewise, openness to patient opinion seems to encourage NICE to accept therapies where the evidence base is relatively weak or the cost effectiveness analysis unfavourable.5 While some decisions by NICE lead to high-profile media criticisms supported by parts of the industry and some patient groups, NICE is for politicians a comparatively safe haven from which decisions can be defended in public by those with expertise. It is therefore no stranger in the British NHS but a continuation of attempts to keep clinical decisions away from politicians, even though they sometimes cannot resist becoming embroiled. Among NICE's political weaknesses are the unrealistic signals that it can send about affordability to politicians and the public and its absence from debates about prioritization.6 The decisions over which services or therapies will be displaced by new treatments approved by NICE are made at local level, whilst cost-effectiveness judgements are made nationally. There is a risk is that therapies may be displaced that are more cost effective than those being introduced, which means that a methodology is now needed to decide how best to disinvest from relatively ineffective but well-established treatments.7 Such arguments about the applicability and implementation of NICE guidelines are, as Gupta and Warner point out, currently central to both clinical governance and commissioning at local level, and have different implications for social services,8 social care,9 nursing10 and general practice.11 Although ‘only in research’ decisions are often seen as rejections12 designed to evade appeals and pressure from lobby groups, their purpose is to generate the additional evidence to allow confident decisions to be made. Influencing the research agenda is not just a good intention, but now has operational expression in research networks designed to facilitate large trials, and in funding streams that supplement industry-funded studies. In the field of dementia, the Dementia & Neurodegenerative Diseases Research Network (DeNDRoN) supports clinical trials and the National Institute of Health Research has recently funded three five-year programmes of projects focusing on non-pharmacological interventions. We are approaching an integrated system of research and development, informed by NICE's assessments. NICE is certainly ‘here to stay’ (JRSM 2007;100:439)13 partly because it is an organization with very significant intellectual resources at its disposal that is capable of rapid learning. More importantly, it is able to set the agenda for the development of new treatments as well as to evaluate their cost effectiveness, and before long is likely to look beyond the specific therapy under review to the wider system of health services provision. We should look forward to this.

On Planing Machine Engineering Characteristics and Machined Timber Surface Quality

Rotary machined timber surfaces exhibit small waves orthogonal to the timber feed direction resulting from the intermittent engagement of the cutting tool with the timber. These surface waves are typically less than five micrometres in height and when regularly spaced at 1 mm width characterize a good quality machined surface. Variations in the regularity of these surface waves are considered as surface defects. Machined timber surfaces produced by planing and moulding machines are a typical case. These surfaces will often exhibit waviness defects caused by inaccurate contact between the tool tip and the timber being cut. There are a number of different vibration sources on these machines. The primary cause of surface waviness defects has been found to be forced vibration, although inaccurate cutter servicing and relocation are also factors. The work presented in this paper concentrates on phenomena caused primarily by forced structural vibration. Systematic engineering and wood machining investigations are applied to a special purpose instrumented test rig so that correlation between vibration data and observed waviness defects can be established. The surface assessment of machined timber is carried out using a special purpose contact based surface tracing instrument. The engineering design and manufacturing influences that lead to unacceptable surface waviness variation effects are discussed.

Clinical learning environments for student nurses: Key indices from two studies compared over a 25 year period

In 1978, a longitudinal study commenced in England to illuminate criteria for the evaluation of hospital wards as clinical learning environments for student nurses. It derived measures to quantify the clinical learning experienced by 71 students in three cohorts in three training hospitals over their entire programme. In 2003, a second study, based in one English School of Health Studies, using clinical placements in three NHS trusts, employed a retrospective, cross-sectional, analytic survey design with anonymised, self-completion questionnaires, to map the clinical learning of 272 students as part of a quality assurance and enhancement initiative. This paper explores changes over time by comparing data based on five key indices, devised in the first study and revisited in the second. Concepts of clinical learning and supervision are reviewed as part of this changing context and background together with limitations implicit in the comparison. The findings suggest an average 20% improvement in the quality of hospital based clinical learning environments over a 25 year period, based mainly on trained staff personally supervising students more extensively, testing their theoretical knowledge more frequently and spending more time performing practical procedures with them. However, unacceptable variations in clinical learning opportunities persist for some students.

The development of an Integrated Care Pathway for all patients with advanced life-limiting illness ? the Supportive Care Pathway

To describe the development and implementation of an Integrated Care Pathway for all patients with advanced life-limiting illness who have been admitted to hospital. This pathway, called the Supportive Care Pathway, has been developed not only in response to the national drivers to improve end of life care, but also in recognition of local survey data which demonstrated the need for strategies to support the provision of palliative care. The pathway is aimed primarily at generalist staff who may have a significant number of patients with palliative care needs on their wards, though not necessarily yet in the last days of life. The pathway, which is being piloted on three elderly care wards in the West Midlands, has been developed in line with accepted Integrated Care Pathway methodology and is being evaluated using the Integrated Care Pathways Assessment Tool. The pathway has been well received by staff using it and early evaluation of its effect in improving documentation of care is encouraging. Unacceptable variations in care for those nearing the end of life is recognized. It is believed that the use of the Supportive Care Pathway may help to reduce that variation by identifying and supporting patients thought to be in the last year of their life.

Identification of Protein Expression Signatures Associated with Helicobacter pylori Infection and Gastric Adenocarcinoma Using Recombinant Antibody Microarrays

Antibody microarray based technology is a powerful emerging tool in proteomics, target discovery, and differential analysis. Here, we report the first study where recombinant antibody fragments have been used to construct large scale antibody microarrays, composed of 127 different antibodies against mostly immunoregulatory antigens. The arrays were based on single framework recombinant antibody fragments (SinFabs) designed for high on-chip stability and functionality and were used for the analysis of malignant and normal stomach tissue samples from Helicobacter pylori-positive and -negative patients. Our results demonstrate that distinct tumor- as well as infection-associated protein expression signatures could be identified from these complex tissue proteomes, as well as biomarkers such as IL-9, IL-11, and MCP-4, previously not found in these diseases. In a longer perspective, this study may improve the understanding of H. pylori-induced stomach cancer and lead to development of improved diagnostics.

Making foot care a priority

One of the main drivers in the development of the National Service Framework (NSF) for Diabetes (Department of Health (DH), 2001a) was the need to reduce inequalities of service provision. The problem was that there were, and still are, unacceptable variations in treatment, as well as in the outcomes of that treatment across England. According to an analysis of the latest Quality and Outcomes Framework (QOF) data from primary care, this variation in diagnosis and treatment is still continuing. For example, the percentage of patients with diabetes with a record of the presence or absence of peripheral pulses in the previous 15months varies from 50.7% to 99.2% between PCTs (National Diabetes Support Team (NDST), 2006). More information on the QOF data relevant to diabetes care can be seen at www.diabetes.nhs.uk/downloads/Factsheet_QOF.pdf .

Quality aspects of prenatal cytogenetic diagnosis: determining the effect of various factors involved in handling amniotic fluid and chorionic villus material for cytogenetic diagnosis

To investigate the effect of factors involved in cell culturing and slide preparation of amniotic fluid (AF) and chorionic villus biopsies (CVB) for prenatal cytogenetic diagnosis. The effect on the outcome of our standard AF cell culture procedure of volume and appearance of the submitted AF specimen, gynaecologist performing the amniocentesis, week of gestation in which the specimen was taken and culture medium was retrospectively investigated. In a prospective study controlled experimental variation was introduced in composition of fixative, relative humidity, temperature and airflow during slide preparation from primary CVB and AF in situ cultures. For evaluation, analysis of regression or variance was used. Provided that at least 0.8 mL AF per culture dish was admitted, none of the investigated factors appeared as critical resulting in unacceptable variation in outcome. Variation in appearance of the AF had a relatively major impact: bloody or brown AF resulted in a 3 days longer culture time. To a limited degree, metaphase quality of AF and CVB cells was affected by composition of fixative, relative humidity, ambient temperature and airflow during slide preparation. Current prenatal cytogenetic practice as described here appears in general to be robust and reliable. The investigated conditions are not critical within the investigated range. Expensive measures for fine control of these conditions are, therefore, not required.