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Background: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients., Methods and Results: Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose-response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative., Conclusion: Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.

Objective:  To monitor the effectiveness of the cervical screening programme and identify suboptimal management in order to improve patient care., Design:  Retrospective study., Setting:   A university hospital serving a population of 1 million people., Population:  All women diagnosed with a cervical cancer between 2003 and 2006., Methods:   Analysis of data from invasive cervical cancer reviews., Main Outcome Measure:  Categorisation of cervical cancer cases according to the Invasive Cervical Cancer Audit classification., Results:   Eighty-seven women were diagnosed with cervical cancer during the 3-year study period. The 'lapsed attender' group accounted for the greatest number of cases (30%), followed by screen detected (26%), interval cancers (13%), never attended (12%), lost to follow-up (10%) and never invited (9%). Women who had never attended for cytology presented with higher stage disease, stage-II or above, compared with the screen-detected cases: 60% were stage II or above, compared with 13.0%, Chi-square P = 0.018. The most frequently identified screening programme problem was patient compliance, which was determined to be the principle contributing factor in 39 cases (45%) and a secondary factor in a further ten cases., Conclusions:  The categorisation of cervical cancer cases has the potential of yielding invaluable information for improving programme effectiveness. Patient compliance is the greatest challenge to the screening programme, and the need for regular screening and adherence to follow-up regimens needs to be reinforced in order to maximise the efficacy of the national screening programme.

Background: Neonatal hyperbilirubinaemia is a common treatable cause of brain injury. The treatment for this condition is phototherapy. The decision whether to use phototherapy is currently dependent upon serum bilirubin assay results. However, repeated blood sampling is not only traumatic but may also be a cause of anaemia in neonates. We evaluated a transcutaneous bilirubin assay method to determine whether it was suitable for routine use in preterm infants., Methods: One hundred and eighty-three transcutaneous bilirubin measurements were taken contemporaneously with blood samples for laboratory measurement of serum bilirubin. The study was carried out with informed parental consent and approval by the local research ethics committee., Results: The transcutaneous bilirubin method (BiliChek) exhibited a consistent positive bias compared with the laboratory bilirubin assay. Consequently, for a given detection rate, the transcutaneous method had a higher screen positive rate, i.e. more neonates would be given phototherapy if transcutaneous bilirubin results were used to decide. There was a margin of safety in the transcutaneous bilirubin assay calibration., Conclusion: The BiliChek transcutaneous bilirubin assay is a safe alternative to laboratory bilirubin assay in deciding whether to give preterm neonates phototherapy.

Background: The current paradigm for cardiovascular risk screening is one of screen and treat; i.e. a risk calculation is used to screen the population to determine who should receive therapy. This is marginally effective with somewhere between 199 and 999 people receiving lipid-lowering therapy and consequently being exposed to the drug-related risk without receiving any benefit., Hypothesis: New evidence suggests that a diagnostic test could be applied to decide which patients will benefit from treatment., Conclusion: Changing the paradigm from 'screen and treat' to 'screen, diagnose and treat' could save large amounts of money by avoiding drugs and could prevent many people from being exposed to side effects.

Background: The diagnosis of copper deficiency and excess states is challenging. It was hoped that the non-caeruloplasmin-bound ("free") copper would reduce this difficulty; however, it has its own problems. The copper/caeruloplasmin ratio has been advocated as an alternative index of copper status, especially as it would not need gender-derived or age-derived reference intervals. However, there are no comparative data for different populations using different assays., Method: Independent paired copper and caeruloplasmin data were retrospectively obtained for three laboratories. From these data, the copper/caeruloplasmin ratio was calculated, and descriptive statistics for the populations and methods were obtained. The relationship between the copper/caeruloplasmin ratio and both copper and caeruloplasmin were also investigated for the three laboratories., Results: All three datasets displayed a non-Gaussian distribution. The Burton median was statistically different from the two other medians, which did not differ significantly from each other. The regression lines for both copper and caeruloplasmin with the ratio differed from each other., Conclusion: The copper/caeruloplasmin ratio behaves differently depending on the laboratory, the population studied, or both. Thus, cut-offs in the literature are not transferable. Each laboratory should therefore derive its own cut-offs.

Background: In Down's syndrome screening, the change in analyte concentrations in maternal serum with advancing gestational age is compensated for by converting concentration to multiples of the median (MoM) by using a mathematical equation describing the expected relationship. However, owing to assay drifts and shift, the equation may be incorrect, leading to deviation of the observed MoM distribution from the ideal MoM distribution. The NHS Fetal Anomaly Screening Programme has produced standards limiting acceptable deviation, and has provided the Down's Syndrome Screening Quality Assurance Service (DQASS) to monitor it. DQASS recommends monitoring by cumulative sum plot., Methods: Down's screening data for 61,368 consecutive samples (12 October 2004 to 31 December 2007) was evaluated using different median assignment techniques., Results: A change in the paradigm for median equation derivation is described, which significantly improves the probability that medians will be correct at any point in time., Conclusion: Software developers need to change the way medians are derived in their programmes.

Medicine has changed from being a reactive process that attempts to alleviate disease only when it is clinically evident to a proactive one in which it is hoped that early intervention may reduce the impact of disease or even it developing at all. In moving the focus of treatment, this inevitably means that a greater number of individuals with lesser disease burdens are treated. The logical end-point of this process is to provide preventative measures for the entire population but this can only be done if the economic costs and negative effects of treatment are out-weighed by the benefits. In the case of pressure ulcers, it is self-evident that prevention is extremely beneficial to patients. However, the cost of some of the equipment used for prevention can be high, and therefore, the balance between the optimum level of provision, the purposes of prevention and the available funding becomes critical. Consequently a screening mechanism to better match susceptible patients with resources is essential. There are, however, many problems with such screening techniques. By looking at other specialties, we can see that it is vital to know the natural history of the disease: PSA testing reveals many men who would have died never having known they had prostate cancer, thus giving them years of worry and morbidity they would probably not previously have suffered; cardiovascular risk screening is so imprecise that risk estimates are of questionable utility; antenatal Down's syndrome risk screening is prone to data-related problems that can unexpectedly reduce the effectiveness of the test. In pressure ulcer screening, there are many tools currently in use, but few (possibly none) are really effective. Finally, this paper details some suggestions for future research to combine risk tests that may offer a prospect for improving ulcer risk screening tools.

Objective: Choice of parameter sets used to calculate Down's syndrome risks is complicated. Published population statistics were compared with assay-specific parameters to optimise screening efficiency., Design: Weight-corrected Gaussian population statistics for alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE(3)), expressed as log(10) multiples of median (MoM) were established for a Belgian cohort of 748 unaffected pregnancies. Using Cuckle's method and Access-specific data, Down's syndrome parameters were tailored to the Belgian cohort. Correlated marker triplets for affected and unaffected pregnancies were modelled and combined with maternal age to calculate term risks for Trisomy 21. Receiver-Operator-Curve (ROC) analysis was performed to identify the optimally-performing population set., Results: Log-normal distributions for the Access markers had geometric mean MoM values close to zero and standard deviation values equal to 0.1460 (AFP), 0.2185 (HCG) and 0.1317 (uE(3)). Correlation between AFP and other markers was significant (p < 0.001). Correlation between HCG and uE(3) was not significant (p = 0.4818). The median ratio between the lowest and highest risk outcomes for the test MoM set was 4.3. Areas under ROC curves differed significantly (p < 0.001) between the models and the analyser-assay specific parameters resulted in the largest area. At a 1 in 250 threshold, sensitivity and specificity were 69% and 96%. At false-positive rates (1-specificity) = 5%, sensitivity was 72.5%., Conclusion: Population parameters significantly affect risk outcome and hence screening performance. Highest efficiency may be obtained with parameters tailored to an assay-specific population model. Consequently models from literature, without knowledge of the assay/analyser combination may lead to suboptimal performance.

The aim of this study was to assess the level of understanding of the role of the tumor marker CA125 in ovarian cancer among doctors of different grades specializing in obstetrics and gynecology (O&G), medicine, surgery, and primary care (general practitioners [GPs]). The study involves a questionnaire-based survey. Two hundred and fifty-nine questionnaires were distributed. An overall response rate of 47.1% was achieved. All grades of doctors and all major specialties were represented. There was a significant difference in the level of self-reported CA125 ordering between the medical specialties, O&G being the most frequent users and primary care the least (P < 0.001), and between the grade of doctors, senior house officers/preregistration house officers and GPs less than consultants and middle grade doctors (P < 0.001). Electronic literature was the first source of advice for the majority of respondents (38.5%). The knowledge of false-positive causes for a raised CA125 was low in medicine, surgery, and primary care specialties, as was the awareness of the sensitivity and specificity of CA125 in epithelial and nonepithelial ovarian cancers. The role of CA125 in ovarian cancer is poorly understood, especially among doctors working outside O&G. Guidelines should be developed to aid clinicians from all specialties in the most appropriate application of CA125 in their practice. Substantial cost savings could be made by the introduction of clear protocol-driven ordering in an attempt to reduce the number of inappropriate tests performed.

Introduction: The biochemical assessment of copper status is not easy when investigating deficient and excess states. Most clinicians request copper and ceruloplasmin and assume that the results provided by their local laboratory are comparable with data in the literature., Aims and Methods: We decided to obtain paired copper and ceruloplasmin values retrospectively from the laboratory information systems from three different hospital laboratories to see how the relationships compared. Descriptive statistics and the relationship between caeruloplasmin and copper were obtained., Results: Our data shows differences in the relationship (slope, intercept and correlation co-efficient) between copper and ceruloplasmin; this is especially the case at the clinical cut-off of a ceruloplasmin concentration of 200 mg/l., Conclusion: Differing methods or populations may be contributing to the differences between the data sets. We therefore recommend that local cut-offs are derived for the investigation of copper deficiency and excess states.

This sixth best practice review examines four series of common primary care questions in laboratory medicine: (1) laboratory monitoring in hypertension and heart failure abnormalities; (2) markers of inflammatory joint disease; (3) laboratory investigation of chronic diarrhoea; and (4) mumps and chickenpox. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus based rather than evidence based. They will be updated periodically to take account of new information.

This fourth best practice review examines four series of common primary care questions in laboratory medicine are examined in this review: (1) safety monitoring for three common drugs; (2) use of prostate-specific antigen; (3) investigation of vaginal discharge; and (4) investigation of subfertility. The review is presented in question-answer format, referenced for each question series. The recommendations represent a precis of the guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most of them are consensus based rather than evidence based. They will be updated periodically to take account of new information.

Background: An investigation on copper metabolism usually includes the measurement of serum levels of copper and caeruloplasmin. Using these levels, some laboratories derive levels of non-caeruloplasmin-bound copper (NCC); however, a considerable number of patients may show negative values, which is not physiologically possible., Aim: To derive an equation for adjusted copper in a manner similar to that widely accepted for adjusted calcium., Methods: A linear regression equation for the relationship between caeruloplasmin and copper was used: [copper] (micromol/l) = 0.052x[caeruloplasmin] (mg/l). An equation for copper adjusted for caeruloplasmin was derived using this equation and the reference interval of 10-25 micromol/l for copper., Results: The derived equation was [adjusted copper] (micromol/l) = [total copper] (micromol/l)+0.052x[caeruloplasmin] (mg/l)+17.5 (micromol/l). The adjusted copper concentrations on the 2.5th and 97.5th centiles were 12.7 and 21.5 micromol/l, respectively, with the population having a gaussian distribution. The relationship between NCC and the adjusted copper concentrations is linear and independent of caeruloplasmin concentration., Conclusion: Calculation of copper adjusted for caeruloplasmin uses the same variables as those for NCC. Accordingly, the problems that are caused by the lack of specificity of caeruloplasmin immunoassays are the same as those identified for NCC. This calculation, however, overcomes the negative values that are found in a considerable minority of patients with NCC, as well as age and sex differences in the caeruloplasmin reference interval. As the concept is already familiar to non-laboratory healthcare professionals in the form of calcium adjusted for albumin, this method is potentially less confusing than that for NCC.

This best practice review examines four series of common primary care questions in laboratory medicine: (i) "minor" blood platelet count and haemoglobin abnormalities; (ii) diagnosis and monitoring of anaemia caused by iron deficiency; (iii) secondary hyperlipidaemia and hypertriglyceridaemia; and (iv) glycated haemoglobin and microalbumin use in diabetes. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards, but form a guide to be set in the clinical context. Most of the recommendations are based on consensus rather than evidence. They will be updated periodically to take account of new information.

Background: Adjusting maternal serum markers for maternal weight is considered to be a standard practice when screening for pregnancies associated with Down's syndrome. The choice of model for taking maternal weight into account is, however, rarely explicitly evaluated., Method: The relationship between the maternal serum markers alphafetoprotein (AFP), human chorionic gonadotropin (HCG) and unconjugated oestriol (uE3), determined with the Beckman Coulter access reagents and maternal weight was investigated in a cohort of 752 Belgian women being screened for pregnancy associated with Down's syndrome. Two different models (the log-linear equation and the linear-reciprocal equation) were used to determine the relationship between the serum markers and maternal weight., Results: A significant relationship between log(10) multiples of median (MoM) values and weight (kg) was obtained for all markers, and the log-linear model had higher coefficients of determination (r(2)) when compared with the linear-reciprocal model. Weight correction with either method achieved the optimum effect that the correction factor for a woman with a population median weight of 65.5 kg was not significantly different from 1. Simulated weight-corrected MoM values with the two approaches were compared and variation was estimated. The mean difference between the weight-corrected MoM values calculated by the two methods was 7.8% (SD 4.3%) for AFP, 14.0% (4.4%) for HCG and 5.9% (3.2%) for uE3. This resulted in a difference in risk estimate of 1.66-5.34% for Down's syndrome owing to weight correction algorithm differences in women of median weight., Conclusion: The log-linear weight correction approach was shown to be marginally more effective by a goodness-of-fit analysis. Differences in weight-corrected MoM values estimated with the two approaches are highly significant (p<0.0001, Wilcoxon's paired sample test), but the effect on risk calculation was not significant. It was observed that the changes in risk became significant the more the MoM correction factors deviated from 1.

Background: Pressure ulcers represent a major cost to the healthcare systems of the world but preventative measures are expensive and could be better targeted. Current risk screening mechanisms are often subjective and could be improved., Aims: To evaluate whether a biochemical assessment tool (Prognostic Inflammatory and Nutritional Index; PINI) based on measurement of albumin, alpha1-acid glycoprotein, C-reactive protein, and prealbumin is of value in estimating the prognosis of patients with pressure ulcers of European Pressure Ulcer Advisory Panel grade 1 and above., Methods: Serum samples were collected from patients participating in a clinical trial of a pressure ulcer preventing mattress. These were analysed for the markers listed above and the PINI calculated. PINI was then evaluated against patient outcome., Results: A statistically significant difference between PINI values in patients whose pressure ulcers improved and those whose ulcers worsened was found in parametric testing, but significance was not achieved in non-parametric testing. A receiver operating characteristic plot showed the PINI was superior to chance in estimating prognosis., Conclusions: The PINI appears to offer a potential route to improving pressure ulcer risk estimation and thus allocation of scarce equipment to improve prevention.

Clinical Guideline CG3 from the National Institute for Health and Clinical Excellence (NICE) makes recommendations on appropriate clinical practice in preoperative testing for elective surgery. Unfortunately, there is minimal evidence on which the guidelines could be based and therefore they were constructed on the basis of professional opinion. This resulted in the construction of a decision matrix of Byzantine complexity built on foundations of sand: surgical risk is estimated using an unvalidated ad hoc risk estimation method; anaesthetic risk is estimated using the American Society of Anesthesiologists (ASA) risk method that has been demonstrated to be incapable of generating consistent risk assessments. The resultant matrix may be suitable for use as a template for future research, but is extremely complex and inadequately rigorous for routine use.

It is vital to evaluate the visual appearance of a wound when considering potential management options. However, where human vision lacks precision, image analysis has been shown to offer a more reliable method of assessment.

Background: CA125 is a high molecular weight glycoprotein, which is expressed by a large proportion of epithelial ovarian cancers. The sensitivity and specificity of CA125 are poor and there are no guidelines produced by the Royal College of Pathologists or the Association of Clinical Biochemists to aid clinicians and laboratories in its most appropriate use., Aim: To identify the patient population having a CA125 measurement and to determine its contribution to individual patient management., Methods: A retrospective case note audit looking at patients who had a CA125 measurement performed between April 2000 and April 2002., Results: The study comprised 799 patients; 751 (94%) were female and 48 (6%) male; 221 (29%) females and 22 (46%) males had an abnormal result. CA125 was mainly used to investigate a wide range of signs and symptoms, and few tests were for follow up or screening of ovarian cancer. In female patients having a CA125 for suspicion of malignancy/ovarian cancer, only 39 (20%) of the abnormal results were caused by ovarian cancer. False positive results were largely caused by another malignancy (48 cases; 26%), benign ovarian disease (26 cases; 14%), and benign gynaecological conditions, particularly leiomyomas (18 cases; 9%). The specificity of CA125 for ovarian cancer increased with concentrations >1000 kU/litre., Conclusions: These results confirm the high false positive rate and poor sensitivity and specificity associated with CA125. The substantial inappropriate usage of CA125 has led to results that are useless to the clinician, have cost implications, and add to patient anxiety and clinical uncertainty.

Renal stones have afflicted humans for millennia but there is still no solution to this problem. This review discusses the laboratory and metabolic aspects of the clinical management of patients with renal stones, both primary and secondary in origin. First, non-pharmacological interventions such as increased fluid intake, decreased protein consumption, dietary changes in sodium, calcium, oxalate, potassium, purine, vitamins, and essential fatty acids are considered. Then specific pharmacological treatment to modify urine calcium, oxalate, urate, citrate, and acidity are considered. Finally, more unusual types of stone are examined.

Background: The majority of variant and abnormal haemoglobins are clinically silent but may not be biochemically silent when it comes to HbA1c estimation., Case Report: We describe several cases in which there were problems in the determination of HbA1c for monitoring diabetes in patients that would not normally be classified as being at risk. Four of these cases were sufficiently unusual to warrant individual publication but all came from a very restricted geographical area with a population of only approximately 500,000. The significance of this is not that variant haemoglobins affect HbA1c analysis but that the occurrence of unexpected/unusual variant haemoglobins may be more frequent than most clinicians would expect, considering that only a small proportion of the basal population are diabetic and have their HbA1c monitored. Differences will exist between different areas due to differences in both the prevalence of variants and the analytical methods employed., Conclusions: Consequently, we propose greater interaction between diabetologists and the laboratory in an attempt to identify these clinically but not biochemically silent variants to achieve a true estimation of the glycaemic control in affected patients.

An 82 year old woman was admitted with worsening dyspnoea. Arterial blood gases were taken on air and revealed a pH of 7.39, with a partial pressure of CO2 (pCO2) of 1.2 kPa, pO2 of 19.3 kPa, HCO3 of 13.8 mmol/litre, and base excess of -16.3 mmol/litre: a compensated metabolic acidosis with hyperventilation induced hypocapnia, which is known to be a feature of lactic acidosis. There was also an increased anion gap ((Na140 + K4.0) - (Cl 106 + HCO3 13.8) = 24.2 mEq/litre (reference range, 7-16)), consistent with unmeasured cation. Lactate was measured and found to be raised at 3.33 mmol/litre (reference range, 0.9-1.7). After exclusion of common causes of lactic acidosis Atorvastatin was stopped and her acid-base balance returned to normal. Subsequently, thiamine was also shown to be deficient. The acidosis was thought to have been the result of a mitochondrial defect caused by a deficiency of two cofactors, namely: ubiquinone (as a result of inhibition by statin) and thiamine (as a result of dietary deficiency).

Background: A previous survey has highlighted the fact that most individuals in chemical pathology identifiable from specialist society membership failed to publish material in Medline cited journals during a five year period. It could be considered that published research that is not cited in other work is not useful unless it has achieved visibility, as demonstrated by citation in another research publication., Aims: To determine whether the frequency of research publication is associated with research visibility., Methods: A random selection from the previous survey was investigated to determine whether the frequency of research publication is associated with research visibility., Results: There was a logarithmic relation between the frequency of publication and visibility, with an increasing probability of citation as publication frequency increases., Conclusions: If academic activity is to survive then individuals must stay active in research; this requires a continuing commitment to a tradition of support for individuals at all stages of their careers engaging in research.

Background: Screening for Down's syndrome forms part of routine obstetric practice. Ethical considerations relating to genetic screening form a major part of the workload of research ethics committees. This study investigated the attitudes of research ethics committee members to several conditions varying in clinical severity and prognosis, including Down's syndrome., Methods: The members of 40 randomly chosen research ethics committees were surveyed. A simple questionnaire comprising 19 clinical scenarios based around four "clinical" conditions was designed to review conditions that were potentially embarrassing, affecting life span but not mental ability, premature death, and intellectual impairment with a risk of neonatal cardiac defects (Down's syndrome). Screening tests with different degrees of effectiveness were described and the diagnostic test descriptions ranged from having no risk to an unaffected fetus to causing spontaneous abortion of two normal fetuses for each affected fetus identified. Replies were graded on a scale of 1 to 5., Results: Seventy seven replies were received from 28 different research ethics committees. Screening was supported for treatment of a life threatening condition (95% in favour) but screening for conditions of a slight increase in premature death (14% in favour) or cosmetic features (10% in favour) were considered unethical. Views were ambiguous (49% in favour) about conditions involving significant shortening of lifespan. Down's syndrome screening was considered more ethical when described as a serious condition (56% in favour) than when the clinical features were described (44% in favour). Once increased rates of spontaneous abortion on confirmatory testing were added, 79% (21% in favour) and 86% (14% in favour) stated that screening was unethical (for "serious" and "clinical features" descriptions, respectively)., Conclusions: Down's syndrome screening raises ethical concerns about genetic testing in general that need to be dealt with before the introduction of any prenatal screening test.

A randomized comparison trial was carried out at Queen's Hospital, Burton-on-Trent, to compare patient outcomes on the RIK mattress (KCI) and the Nimbus 3 mattress (Huntleigh Healthcare). One hundred and fifty-eight patients, who were assessed to be at particular risk of development of pressure ulcers using the Waterlow score (85 on RIK mattress, 83 on Nimbus), completed the trial. There were no statistically significant differences in baseline parameters at recruitment or pressure ulcer progress. Lack of difference can be as useful as evidence of superiority. Other factors such as nursing interventions required accessible equipment, and costs are important when making equipment choices. For a significant proportion of patients, a static (RIK) mattress can be as effective as an active (Nimbus 3) mattress for management of pressure ulcers.

Aims: To investigate the research productivity of all staff in chemical pathology., Methods: Chemical pathologists or biochemical scientists were identified from publicly available sources. All journals, their impact factors (IFs), and individual publications over the period of 1995 to 1999 were identified from electronic databases. Each publication was subclassified with respect to type of publication, number and position of author, and subspecialty to which the article referred., Results: Research output over the period comprised 6162 articles, originating from 1399 individuals, 264 of whom were medically qualified. Specialty initiated research accounted for 26% of the total publications and 80% of the research was performed in teaching hospitals. Research output was highly skewed because 49% of individuals published a letter or more, 20% published one original piece of research over five years, but only 4% were research active, as defined by one publication each year. International standard research, defined as one paper each year in journals with IF > 4, was achieved by 1% of the profession, mostly aged > 55 years. Skewed distributions of publication rates were found in all age deciles. The possession of higher research degrees correlated with higher output in all age deciles., Conclusions: Those working in chemical pathology are active in initiating and conducting research, although at a low level. Because longterm activity in research correlates with the possession of higher research degrees and the opportunity to carry out research from early in career pathways, priority should be given to encouraging research in training, given the small and ageing profile of international quality research in the profession in the UK.

We report a descriptive study using a questionnaire and twelve digital photographs classified by a consensus panel of experts using the European Pressure Ulcer Advisory Panel and Stirling plus digits classifications. The expert panel comprised 5 tissue viability specialists/clinical lecturers in tissue viability with many years of collective experience and examined 30 images over 2 1/2 hours. In general consensus on wound grading was good; in only 2 images was there insoluble disagreement. Two hundred subjects were recruited from a Tissue Viability Society (N = 50), the European Pressure Ulcer Advisory Panel (N = 50), five Community Trusts (N = 50) and five Acute Trust (N = 50) in England and Wales. The subjects were asked for demographic details (qualifications achieved, number of years qualified, employment grade and how their knowledge of classification of pressure ulcers has been obtained). The second part of the questionnaire asked them to classify twelve digital photographs of pressure ulcers using the European Pressure Ulcer Advisory Panel (EPUAP) and the Stirling plus digits systems. The study demonstrated that there is considerable lack of consensus when pressure ulcers are graded using the Stirling plus digit grading system and less disagreement when the EPUAP scale is used. The study also demonstrates that the statistical returns from different hospital and community units cannot be considered to be directly comparable. Furthermore, the study showed that the nurses most educated in pressure ulcer care (Clinical Nurse Specialists in Tissue Viability) were the most keen to receive extra education, whilst ward nurses were happy with their current knowledge and did not believe further education on pressure ulcer grading was necessary.

Nutrition is vital to all bodily processes. During wound healing, it is essential that nutrients are available as they form the building blocks for tissue repair. Nutrition may therefore affect healing due to an overall deficiency of intake, either due to non-availability or due to inability of the patient to absorb sufficiently to meet their requirements. Alternatively, deficiencies of specific nutrients may also inhibit healing and on the converse some additives, not normally present in large quantity in the diet, may have beneficial effects. This review considers the nutritional factors affecting wound healing and some developments that may alter the future of therapy.

By 1998, most health authorities offered antenatal screening for Down's syndrome, usually by biochemical methods. To date, the development of this form of screening has not been coordinated by a national body and, consequently, there are wide variations in practice between localities. Fortunately, many of these variations have not led to any noticeable inequality of health provision, but the wide variation in risk cut offs used by different centres does. Other variations merely lead to potentially unnecessary expenditure; whereas it is believed that adding extra tests to the screening procedure is beneficial (such as double test to triple test), statistical evaluation of the confidence intervals for the detection rates quoted indicates that there is no evidence that the extra test provides an increase in detection. The cervical screening programme has progressively improved, partly through the auspices of a national framework. A similar national approach would benefit Down's screening and is only now being considered: the national screening committee (NSC) is currently drafting recommendations. To ensure optimum screening performance, the NSC should specify the risk thresholds applied, the screening protocols to be used--that is, an opt-in programme with a minimum (possibly even a maximum) of two biochemical analytes or a nuchal fold evaluation--and perhaps should even recommend national population parameters to be used for risk calculation. It might even be advisable for statistical work to be carried out to determine whether local derivation of medians is truly necessary. Furthermore, defined options for older women could be specified--for example, should all older patients have the option to proceed directly to amniocentesis if they wish or should National Health Service amniocentesis only be available for those with a "high risk" screening result. The difficulties that will face the NSC in deciding which screening policy to adopt are also considered; specifically, the lack of evidence to suggest that triple testing is superior to double testing, and the lack of evidence to prove the superiority of one analyte over another. This inadequacy of evidence is not from want of trying, but is caused by the problems of collecting enough data to provide statistical significance. Finally, there is one important difference between cervical and Down's syndrome screening that has a major impact on the advice given by any "expert"; namely, patents. Many aspects of Down's screening are subject to patents and, therefore, there is more potential for apparently uncontroversial decisions to rebound with future retrospective patent infringement claims. Thus, it would be sensible to insist that any member of a national body deciding upon Down's screening policy must fully disclose all potential conflicts of interest, both personal and family, before they are allowed to sit on the committee. Furthermore, if a national policy is decided upon, worldwide patent searches should be carried out to determine whether there are any possible unforeseen legal consequences of any recommendation.

Context: Under routine hospital conditions handwashing compliance of health care workers including nurses, physicians, and others (eg, physical therapists and radiologic technicians) is unacceptably low., Objectives: To investigate the efficacy of an education/ feedback intervention and patient awareness program (cognitive approach) on handwashing compliance of health care workers; and to compare the acceptance of a new and increasingly accessible alcohol-based waterless hand disinfectant (technical approach) with the standard sink/soap combination., Design: A 6-month, prospective, observational study., Setting: One medical intensive care unit (ICU), 1 cardiac surgery ICU, and 1 general medical ward located in a 728-bed, tertiary care, teaching facility., Participants: Medical caregivers in each of the above settings., Interventions: Implementation of an education/ feedback intervention program (6 in-service sessions per each ICU) and patient awareness program, followed by a new, increasingly accessible, alcohol-based, waterless hand antiseptic agent, initially available at a ratio of 1 dispenser for every 4 patients and subsequently 1 for each patient., Main Outcome Measure: Direct observation of hand-washing for 1575 potential opportunities monitored over 120 hours randomized for both time of day and bed locations., Results: Baseline handwashing compliance before and after defined events was 9% and 22% for health care workers in the medical ICU and 3% and 13% for health care workers in the cardiac surgery ICU, respectively. After the education/feedback intervention program, handwashing compliance changed little (medical ICU, 14% [before] and 25% [after]; cardiac surgery ICU, 6% [before] and 13% [after]). Observations after introduction of the new, increasingly accessible, alcohol-based, waterless hand antiseptic revealed significantly higher handwashing rates (P<.05), and handwashing compliance improved as accessibility was enhanced-before 19% and after 41% with 1 dispenser per 4 beds; and before 23% and after 48% with 1 dispenser for each bed., Conclusions: Education/feedback intervention and patient awareness programs failed to improve handwashing compliance. However, introduction of easily accessible dispensers with an alcohol-based waterless handwashing antiseptic led to significantly higher handwashing rates among health care workers.

The primary objective of this randomised controlled trial was to determine whether there were significant differences between two pressure-relieving systems. A secondary aim was to investigate whether the availability of extra pressure-relieving equipment would reduce the incidence of ulcers in an acute hospital setting. A total of 141 patients in a care-of-the-elderly unit, who were assessed to have a high risk of developing pressure ulcers using the Waterlow score, were recruited; 70 were nursed using Huntleigh Nimbus 3 in conjunction with the Aura cushion (Group A), and 71 using the Pegasus Cairwave Therapy System in conjunction with the Proactive 2 Seating cushion (Group B). The main outcome measure was visual assessment, supported by a photographic record. There were three main findings: for non-heel ulcers and overall improvement, there was no statistically significant difference between the two products tested; for heel ulcers there was a significant difference (P = 0.019) with more patients healing in Group A than in Group B. The average length of stay of patients who completed the trial was 21.6 days (Group A) and 21.7 days (Group B) for patients completing a live (range 1-121 days) and for patients who died 29.7 days (Group A) and 24.3 days (Group B). Routine monitoring showed that, before the trial, the incidence of hospital-acquired pressure ulcers (Torrance grade 2+) was 0.2%; during the trial, this dropped to 0.13%. The study showed differences in the efficacy of different mattress products; with a sufficiently large study, it is possible to demonstrate statistically significant results. Provision of extra pressure-relieving equipment can reduce the incidence of pressure ulcers but may not influence length of stay.

Objective: To compare nine different algorithms for determining the necessity for drug treatment of hyperlipidaemia in patients without cardiovascular disease., Design: Risk-factor data on 400 patients were obtained. Algorithms assessed included the Framingham model, National Cholesterol Education Program, European, British, New Zealand, British Regional Heart Study, Sheffield, Munster Heart Study and Dundee guidelines and a local general rule for treatment of atheroma (General Rule to Enable Atheroma Treatment)., Setting: Three hospital lipid clinics., Results: Patients were 56% male, aged 53.8 +/- 12.3 years, 38% smoked, 55% had a family history of disease (37% familial hypercholesterolaemia, 33% hypertension and 5.2% left ventricular hypertrophy); 31% were moderately obese and 15% were diabetic. The average cholesterol level was 7.9 +/- 2.6 mmol/l. Median Framingham risk was 1.66%/year and this risk was > 2%/year for 37% and > 3%/year for 17.5%. Treatment was required for 86% by National Cholesterol Education Program, 70% by General Rule to Enable Atheroma Treatment and European, 61% by New Zealand, 58% by British, 42% by Dundee, 40% by Munster Heart Study, 25% by British Regional Heart Study and 16% by Sheffield guidelines. Algorithms varied regarding recommendations for treatment of men, women, patients with familial hypercholesterolaemia and diabetes. Confounders included risk levels, definitions and weightings for additional risk factors., Conclusions: Different algorithms vary widely in their predictions of need for drug treatment of this high-risk population with hyperlipidaemia. Authors of guidelines for cardiovascular disease need to unify risk thresholds and definitions and audit the effects of additional weighting factors so that patients can be treated consistently.