Tim Reynolds

Accuracy of cardiovascular risk estimation for primary prevention in patients without diabetes

Background The burden of atherosclerosis has led to treatment prioritization on high-risk individuals without established cardiovascular disease based on risk estimates. We investigated the effects of biological variation in risk factors on risk estimate accuracy and whether current primary prevention screening (risk assessment) models correctly categorize patients. Methods A population of 10 000 ‘perfect’ individuals with 100 simulants affected by biological and analytical variation for systolic blood pressure, total cholesterol, high-density lipoprotein-cholesterol was mathematically modelled. Coronary heart disease (CHD) risks were calculated using the Framingham study algorithm and the mathematical properties of the screening system were evaluated. Results At internationally recommended 10-year CHD risk treatment threshold levels of 15, 20 and 30%, the 95% confidence intervals were ± 5.1, ± 6.0 and ± 6.9% for single-point (singlicate), ± 3.6, ± 4.2 and ± 4.9% for duplicate and ± 2.8, ± 3.3 and ± 3.9% for triplicate estimates respectively (i.e. for singlicate 15% risk, 95% confidence interval is 9.9–20.1%). Consequently, using the 30% risk threshold from the National Service Framework (NSF) for CHD with singlicate estimation, 30% of patients who should receive treatment would be denied it and 20% would receive treatment unnecessarily. Multiple measurements improve precision but cannot absolutely define risk. Blood pressure should be measured to the greatest accuracy possible and not rounded prior to averaging. Conclusions This study suggests biological variation in cardiovascular risk factors has profound consequences on calculated risk for therapeutic decision-making. Current guidelines recommending multiple measurements are usually ignored. Triplicate measurement is required to allow risk to be identified and clinical judgement has to be exercised in interpretation of the results.

How Accurate are pressure ulcer grades? An image-based survey of nurse performance

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.

Preoperative Axillary Staging in Breast Cancer—Saving Time and Resources

Abstract:  This study was performed to assess the feasibility and accuracy of ultrasound guided fine needle aspiration biopsy for axillary staging in invasive breast cancer. Data were collected prospectively from June 2005 to June 2006. In all, 197 patients with invasive breast cancer and clinically nonsuspicious axillary lymph nodes were included. Patients with suspicious nodes on ultrasound had fine needle aspiration biopsy. Those with fine needle aspiration biopsy positive for malignancy were planned for axillary nodes clearance otherwise they had sentinel node biopsy. Patients (41) had ultrasound guided fine needle aspiration biopsy. Three cases were excluded for being nonconclusive. Postoperative histology showed 18/38 cases (47.4%) axillary lymph nodes positive and 20/38 cases (52.6%) axillary nodes negative. Ultrasound guided fine needle aspiration biopsy was positive in 8/38 cases (21.1%), negative in 30/38 cases (78.9%). The sensitivity of ultrasound guided fine needle aspiration biopsy was found to be 47.1%, specificity 100%, positive predictability 100%, negative predictability 70%, and overall accuracy 76.3%. Ultrasound guided fine needle aspiration biopsy was found to be more accurate and sensitive when two or more nodes were involved, raising the sensitivity to 80% and negative predictability to 93.3%. Preoperative axillary staging with ultrasound guided fine needle aspiration biopsy in invasive breast cancer patients is very beneficial in diagnosing nodes positive cases. These cases can be planned for axillary lymph nodes clearance straightaway therefore saving patients from undergoing further surgery as well as time and resources.

Glycated haemoglobin (HbA1c) monitoring.

Glycation of haemoglobin to produce HbA1c occurs throughout the 120 day average lifespan of the red blood cell. Repeat testing in less than 120 days or situations that shorten this lifespan will produce HbA1c results that do not fully reflect current diabetic control

Cholesteryl ester storage disease: a rare and possibly treatable cause of premature vascular disease and cirrhosis

Cholesteryl ester storage disease (CESD) is an autosomal recessive lysosomal storage disorder caused by a variety of mutations of the LIPA gene. These cause reduced activity of lysosomal acid lipase, which results in accumulation of cholesteryl esters in lysosomes. If enzyme activity is very low/absent, presentation is in infancy with failure to thrive, malabsorption, hepatosplenomegaly and rapid early death (Wolman disease). With higher but still low enzyme activity, presentation is later in life with hepatic fibrosis, dyslipidaemia and early atherosclerosis.Identification of this rare disorder is difficult as it is essential to assay leucocyte acid phosphatase activity. An assay using specific inhibitors has now been developed that facilitates measurement in dried blood spots. Treatment of CESD has until now been limited to management of the dyslipidaemia, but this does not influence the liver effects. A new enzyme replacement therapy (Sebelipase) has now been developed that could change treatment options for the future.

Concordance evaluation of coronary risk scores: implications for cardiovascular risk screening.

SUMMARY Objective: To assess the similarities and differences in predicted high-risk individuals identified by different cardiovascular risk calculation algorithms Research design and methods: A representative population of 10 000 individuals was modelled in a computer using baseline data from the National Health Survey for England. The effects of biological variation in each major model parameters were then applied to each hypothetical individual. The predictive capacities of 3 different risk identification systems based on computer calculation (the Framingham algorithm), or on tabular methods (the Sheffield tables and the General Rule to Enable Atheroma Treatment) were evaluated. Results: All three models predict that similar numbers would receive treatment with 2.9 and 10% receiving treatment at 30 and 15% 10 year risk thresholds, respectively. However, concordance is limited as 0.3 or 6.8% are positive on all three systems; 1.6 or 9.7% on any two calculators at the 30 and 15% thresholds, respectively. The risk groups identified by each calculator depend on the baseline assumptions in each model. Conclusion: Care needs to be taken with applying risk calculators to populations different from which they were derived. Any cardiovascular risk scoring system needs to be thoroughly evaluated against epidemiological data before it is introduced and also needs to be updated in line with changing trends in risk factors.

A regression analysis of the Waterlow score in pressure ulcer risk assessment

Objective: To explore the predictive value of the Waterlow score, and the subscores of age and gender. Design: Logistic regression analysis was conducted on the two subscores of the Waterlow score, and the residual Waterlow score with gender and age removed. Receiver operating characteristic (ROC) analysis gave a quantitative measure of the classification ability of the Waterlow score. Setting: Burton, UK. Subjects: All admissions over a five-year period to the District General Hospital, a total of 150 015 admissions of 82 691 patients. Interventions: None. Main outcome measures: Area under the ROC curve for significant (as determined by logistic regression) variables. Results: Data were inaccurate in at least 44.7% of the records, and analysis was conducted on the 43 735 records for which no errors were apparent. Nine hundred and fifty-four patients had a pressure ulcer on admission (2.1%); 277 developed a pressure ulcer (0.6%). The Waterlow score was predictive of pressure ulcers. Age was predictive, and gender was not found to be a significant predictor. Conclusions: The Waterlow score may be improved and simplified by removing gender from the scoring system.

Is Clinical Pathology Accreditation worth it? A survey of CPA‐accredited laboratories

Following two pilot studies, Clinical Pathology Accreditation (CPA) accreditation was introduced to UK pathology laboratories in 1992. Since then, significant numbers of laboratories have undergone accreditation but many have never applied. We carried out a postal survey of 145 accredited laboratories in the UK to independently determine the opinions of laboratory managers/clinicians about CPA and whether accreditation had produced any significant benefits to pathology services. Ninety-three replies were received (64 per cent) a good response to an unsolicited questionnaire. Most laboratories felt accreditation by CPA had resulted in better laboratory performance with more documentation and better health and safety and training procedures. CPA accreditation was believed to provide useful information by approximately 50 per cent of laboratories but was also felt by a significant proportion of laboratories to be over-bureaucratic, inefficient and expensive (46 of 93 respondents). Many complaints were voiced about the excessive paperwork that CPA generated and there was also a significant body of opinion that felt that CPA assessed areas were the domain of other regulatory bodies such as the CPSM, IBMS and HSE.

Copper:caeruloplasmin ratio

Investigation of copper status can be a diagnostic challenge. The non-caeruloplasmin-bound copper (NCC) has deficiencies; accordingly, the copper:caeruloplasmin ratio has been suggested as an alternative index of copper status. A reference interval for this index was derived. In addition to making the interpretation of copper easier, the copper:caeruloplasmin ratio should also enable adjustment for relatively high caeruloplasmin concentrations without recourse to producing gender- and age-derived intervals. The copper:caeruloplasmin ratio has weaknesses similar to those identified for NCC in that immunological methods used for caeruloplasmin can cross react with apocaeruloplasmin and there is no standardised method for caeruloplasmin. Caeruloplasmin assays also have uncertainty from precision, bias and specificity and, accordingly, method-related differences may have a large effect on the copper:caeruloplasmin ratio in a manner similar to the NCC.

Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease

BACKGROUND Connective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CTD often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD. METHODS Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögrens syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA(®) (Memory Lymphocyte Immuno Stimulation Assay). RESULTS In all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (P<0.0001). The most frequent allergens were nickel, mercury, gold and palladium. CONCLUSIONS Patients with SLE, RA and SS have an increased frequency of metal DTH. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in CTDs, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies.