The effectiveness of service delivery initiatives at improving patients' waiting times in clinical radiology departments: a systematic review.

We reviewed the literature for the impact of service delivery initiatives (SDIs) on patients' waiting times within radiology departments. We searched MEDLINE, EMBASE, CINAHL, INSPEC and The Cochrane Library for relevant articles published between 1995 and February, 2013. The Cochrane EPOC risk of bias tool was used to assess the risk of bias on studies that met specified design criteria. Fifty-seven studies met the inclusion criteria. The types of SDI implemented included extended scope practice (ESP, three studies), quality management (12 studies), productivity-enhancing technologies (PETs, 29 studies), multiple interventions (11 studies), outsourcing and pay-for-performance (one study each). The uncontrolled pre- and post-intervention and the post-intervention designs were used in 54 (95%) of the studies. The reporting quality was poor: many of the studies did not test and/or report the statistical significance of their results. The studies were highly heterogeneous, therefore meta-analysis was inappropriate. The following type of SDIs showed promising results: extended scope practice; quality management methodologies including Six Sigma, Lean methodology, and continuous quality improvement; productivity-enhancing technologies including speech recognition reporting, teleradiology and computerised physician order entry systems. We have suggested improved study design and the mapping of the definitions of patient waiting times in radiology to generic timelines as a starting point for moving towards a situation where it becomes less restrictive to compare and/or pool the results of future studies in a meta-analysis.

Are the UK systems of innovation and evaluation of medical devices compatible? The role of NICE's Medical Technologies Evaluation Programme (MTEP).

The economic evaluation of medical products and services is increasingly prioritised by healthcare decision makers and plays a key role in informing funding allocation decisions. It is well known that there are a number of methodological difficulties in the health technology assessment of medical devices, particularly in the provision of efficacy evidence. By contrasting devices with pharmaceuticals, the way in which the differing systems of innovation mould the UK's industry landscape is described and substantiated with market statistics. In recognition of the challenges faced by industry, as well as the growing need for cost-effective allocation of National Health Service (NHS) resources, the National Institute for Health and Care Excellence (NICE) led the development of the Medical Technologies Evaluation Programme (MTEP), which launched in 2009/2010. The review of the UK's medical devices market supports the programme's three principal aims: to simplify access to evaluation, speed up the process, and increase evaluative capacity for devices within NICE. However, an analysis of the output of MTEP's first 3 years suggests that it has some way to go to meet each of these aims.

Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS): a prospective cohort study.

OBJECTIVE: To evaluate mildly abnormal liver function test (LFT) results in general practice among patients who do not have known liver disease. DESIGN: Prospective cohort study of people with abnormal LFT results identified in primary care. Participants were intensively investigated using a common protocol and followed up for 2 years. Substudies investigated the psychological sequelae of abnormal test results, clinicians' reasons for testing, decision options when LFT results were abnormal and early detection of liver fibrosis. SETTING: Eleven primary-care practices: eight in Birmingham and three in Lambeth. PARTICIPANTS: Adults with abnormal LFT results who did not have pre-existing or obvious liver disease. Eight analytes were included in the panel of LFTs. MAIN OUTCOME MEASURES: Statistical tests were used to identify the interactions between clinical features, the initial pattern of abnormal LFT results and (1) specific viral, genetic and autoimmune diseases, such as viral hepatitis, haemochromatosis and primary biliary cirrhosis; (2) a range of other serious diseases, such as metastatic cancer and hypothyroidism; (3) 'fatty liver' not associated with the above; and (4) the absence of detectable disease. RESULTS: Fewer than 5% of people with abnormal LFT results had a specific disease of the liver, and many of these were unlikely to need treatment. The diagnostic potential of the LFT panel is largely subsumed into just two analytes: alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Gamma-glutamyltransferase (GGT) offers a small increase in sensitivity at the margin at the cost of a large loss of specificity. Eighty-four per cent of abnormal LFT results remain abnormal on retesting 1 month later. In many cases, carrying out a definitive or specific test will be more efficient than repeating LFTs, with a view to specific testing only if the test remains abnormal. An ultrasound diagnosis of 'fatty liver' was present in nearly 40% of patients with abnormal LFTs and a small amount of weight loss over 2 years was associated with a reduced incidence of liver fat. There was a J-shaped relationship between alcohol intake and fatty liver in men. An abnormal LFT result causes temporary anxiety, which does not appear to promote sustained behaviour change. CONCLUSIONS: Liver disease is rare among people with abnormal LFT results in primary care. Only two analytes (ALT and ALP) are helpful in identifying the majority of liver disease. GGT adds little information in return for a high false-positive rate but it is sensitive to alcohol intake. LFT results seldom revert from abnormal to normal over a 1-month period, and modelling shows that repeating an abnormal LFT panel, as recommended in the current guidelines, is inefficient. LFTs are often undertaken to meet perceived patient need for a blood test, but as they are neither specific nor indicative of any particular disease they are among the least suitable tests for this purpose. Obesity and raised ALT provide strong evidence for a presumptive diagnosis of 'fatty' liver. Abnormal LFTs and 'fatty' liver provoke only short-term anxiety and neither is associated with sustained weight loss. Even a small amount of weight loss reduces liver fat. FUTURE WORK RECOMMENDATIONS: (1) the cases of 'fatty liver' and controls should be followed up in the long term to identify features that predict development of hepatosteatosis and then cirrhosis; (2) the acceptability of replacing the traditional six- to eight-analyte LFT panel with a drop down menu including the ALT/ALP combination should be evaluated. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Environmental properties of long-chain alcohols. Part 2: Structure-activity relationship for chronic aquatic toxicity of long-chain alcohols.

Daphnia magna reproduction tests were performed with C(10), C(12), C(14) and C(15) alcohols to establish a structure-activity relationship of chronic effects of long-chain alcohols. The data generation involved substantial methodological efforts due to the exceptionally rapid biodegradability of the test substances and the need to test as close as possible to their water solubility limits. Test concentrations were determined by GC-MS before and after test solution renewal. Whereas apparent toxicity based on survival and reproduction increased with increasing C-chain lengths up to C(14), observations of toxicity to C(15) alcohol were not in line with lower chain lengths due to the lack of toxicity below the level of water solubility. When omitting C(15), the slope of most (Q)SARs approach -1, being consistent with the expectation of a non-polar narcotic mode of action. Further testing at higher chain lengths is not sensible due to progressively lower solubility, at remaining biodegradability. Effects on mortality and reproduction are not expected below the level of water solubility.

Clinicopathological features and molecular markers of breast cancer in Jos, Nigeria.

BACKGROUND: Several studies have suggested that breast cancer in black women is associated with aggressive features and poor survival. This study examines molecular markers along with clinical stage and pathological grade in breast cancer material from Jos, Nigeria. STUDY DESIGN: The histological diagnoses of 178 consecutive Nigerian patients with breast cancer were retrieved from their hospital records. A subset of 36 patients was staged and their tumours typed and graded. Immunohistochemical staining of sections from paraffin wax embedded tissues from these cases for the expression of oestrogen receptor (ER), progesterone receptor (PGR), Human ERBB2 (or HER2/neu), p53 and cyclin D1 (CCND1) was carried out using the avidin biotin complex (ABC) procedure. RESULTS: A majority of the cases were invasive ductal carcinoma (92.7%), high grade (grade 3, 70.6%) and of late clinical stage (stages III and IV, 58.3%). Only 25% and 27.8% of cases expressed ER and PGR respectively. The ERBB2 and CCND1 antigens were expressed in 25%, and 5.7% of cases respectively. The p53 protein was the most frequently expressed in this study (47.2% of cases). High grade tumours were significantly more likely to be ER and PGR negative (P = 0.006 and P = 0.002 respectively). CONLCLUSION: There is predominance of high grade, invasive ductal carcinomas which are likely to be ER and PGR negative but p53 positive. These features suggest a biologically aggressive form of breast cancer in Nigerian women with the possibility of poor response to both hormonal therapy and chemotherapy.

Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. All Wales Research into Elderly (AWARE) Study.

OBJECTIVE: To determine whether cognitive impairment is associated with changes in self-care behaviour and use of health and social services in older subjects with diabetes mellitus. RESEARCH DESIGN AND METHODS: This was a community based, case-control study of subjects registered with general practices participating in the All Wales Research into Elderly (AWARE) Diabetes Study. The 396 patients aged 65 years or older with known diabetes mellitus were compared with 393 age- and sex-matched, non-diabetic controls. Adjusted odds ratio estimates of normal performance on Mini-Mental State Examination (MMSE) and Clock Drawing Test (numbers and hands) were determined. Information on self-care behaviours and use of services was obtained. RESULTS: A total of 283 (71%) diabetic subjects scored 24 or more on MMSE, compared with 323 (88%) of controls (OR 0.54, P<0.0005). The mean (S.D.) scores were 24.5 (5.1) and 25.7 (4.3), respectively (difference between means 1.22; 95% CI 0.56, 1.88; P<0. 001). Clock testing demonstrated that 257 (65%) and 286 (72%) diabetic subjects correctly placed the numbers and hands, respectively, compared with 299 (76%) and 329 (84%) of controls (OR 0.59, P<0.001 and P<0.52, P<0.0005, respectively). Both test scores declined with increasing age, earlier school leaving age and deteriorating visual acuity. Of other variables examined, only need for oral hypoglycaemic drugs or insulin, history of stroke, dementia or Parkinson's disease and symptoms of autonomic neuropathy significantly impaired one or more cognitive test scores. The odds ratios (95% CI) for normal cognitive test results in subjects with diabetes after adjusting for all significant variables was 0.74 (0. 56, 0.97), P=0.029 for MMSE scores and 0.63 (0.44, 0.93), P=0.019, and 0.58 (0.38, 0.89), P=0.013, for the numbers and hands parts of the clock test, respectively. In comparison with diabetic subjects with no evidence of cognitive impairment, diabetic subjects with an MMSE score <23 were significantly less likely to be involved in diabetes self-care (P<0.001) and diabetes monitoring (P<0.001). A low MMSE score was also significantly associated with higher hospitalisation in the previous year (P=0.001), reduced ADL (activities of daily living) ability (P<0.001) and increased need for assistance in personal care (P=0.001). CONCLUSIONS: Elderly subjects with predominantly Type 2 diabetes mellitus display significant excess of cognitive dysfunction, associated with poorer ability in diabetes self-care and greater dependency. Routine screening of cognition in older subjects with diabetes is recommended.

Older adults, diabetes mellitus and visual acuity: a community-based case-control study.

MAIN OBJECTIVES: to screen for impaired distance visual acuity in older adults living at home, both with and without diabetes mellitus to determine whether diabetes increases the likelihood of visual impairment and to identify associated factors. DESIGN: case-control study. SETTINGS: three districts of Wales: North Clwyd, Powys and South Glamorgan, with assessments in subjects' homes. SUBJECTS: 385 with diabetes mellitus and 385 age- and sex-matched controls. MAIN OUTCOME MEASURES: visual acuity measures, short form (SF)-36 quality of life scores RESULTS: we observed impairment of visual acuity in 40% of those with diabetes mellitus and 31% of controls. Diabetes was associated with an increased risk of visual impairment [odds ratio 1.50 (95% confidence interval 1.09-2.05), P = 0.013]. The pinhole test identified uncorrected refractive error in 11% of the 63 patients with diabetes and 12% of the 49 controls who wore glasses, and in 51% of the 91 patients and 84% of the 69 controls who did not wear glasses (P < 0.001). Increasing age (P < 0.001) and female sex (P = 0.014) were significantly associated with visual impairment in both groups, whilst history of foot ulceration (P = 0.001), duration of diabetes (P = 0.018) and treatment with insulin (P < 0.001) were significantly associated with visual impairment in subjects with diabetes. We observed a significant association between impaired visual acuity and five domains of the SF-36 (physical and social functioning, mental health, vitality, and health perceptions; P < 0.01 in each case). CONCLUSION: older adults living at home have a high prevalence of uncorrected visual impairment. Diabetes mellitus is associated with significantly increased risk of visual loss. This impairment is associated with detriments in health-related quality of life. We recommend earlier use of optometry services and assessment of visual acuity by clinicians.

Derivation of predicted No-effect concentrations for lindane, 3, 4-dichloroaniline, atrazine, and copper.

Environmental risk assessment is a key feature of regulations controlling the placing of new, and the maintenance of existing, chemicals products in the market place. For example, European Commission Directive 93/67/EC on Risk Assessment for New Notified Substances and Commission Regulation (EC) No. 1488/94 on Risk Assessment for Existing Substances requires that risk assessments be carried out for new and existing substances in the European Community. The process of environmental risk assessment seeks to determine the balance of probability of species and communities being damaged by chemical releases. The process relies upon a valid estimation of a predicted environmental concentration (PEC) in relevant environmental compartments and a predicted no effect concentration (PNEC) below which the organisms present in that compartment are unlikely to be significantly affected. If the PEC exceeds the PNEC there is a potential for damaging effects to occur. This article focuses on the determination of PNECs for risk assessment. Methods for determining a PNEC described in OECD Monograph 26 (1989, Report of the OECD Workshop on Ecological Effect Assessment, Paris, France, have been applied to data derived for the four chemicals lindane, 3,4-dichloroaniline, atrazine, and copper in a series of collaborative research projects funded by the European Commission.

Development of methods to assess the effects of xenobiotics in outdoor artificial streams.

Two collaborative research projects were designed to develop and validate methods for determining the chronic effects of xenobiotics in freshwater ecosystems. The work reported here focuses on the development of methods for measuring effects on fish, invertebrates, and algae in outdoor artificial streams. 3,4-Dichloroaniline (3,4-DCA), has been used as a reference xenobiotic in two artificial stream experiments. The first used five stream channels: a control and treatments ranging from 70 to 2400 microg/liter. The second used eight stream channels--a control and treatments ranging from 0.45 to 4700 microg/liter and four coupled, 510-liter-capacity, downstream ponds-a control and treatments of 1.7, 37, and 820 microg/liter. Effects on the biota of the stream channels and the downstream ponds were examined using a range of sampling techniques and in situ toxicity tests.

Development of methods for evaluating toxicity to freshwater ecosystems.

This article presents a summary of a collaborative research program involving five European research groups, that was partly funded by the European Commission under its Environmental Research Program. The objective of the program was to develop aquatic toxicity tests that could be used to obtain data for inclusion at Level 2 of the Risk Evaluation Scheme for the Notification of Substances as required by the 7th Amendment to EC Directive 79/831/EEC. Currently only a very limited number of test methods have been described that can be used for this purpose and these are based on an even smaller number of test species. Tests based upon algae (Chlamydomonas reinhardi, Scenedesmus subspicatus, and Euglena gracilis), protozoa (Tetrahymena pyriformis), rotifera (Brachionus calyciflorus), crustacea (Gammarus pulex), and diptera (Chironomus riparius) were developed. The tests encompassed a range of end points and were evaluated against four reference chemicals: lindane, 3, 4-dichloroaniline (DCA), atrazine, and copper. The capacity of the tests to identify concentrations that are chronically toxic in the field was addressed by comparing the effects threshold concentrations determined in the laboratory tests with those determined for similar and/or related species and end points in stream and pond mesocosm studies. The lowest no-observed-effect concentrations (NOEC), EC(x), or LC(x) values obtained for lindane, atrazine, and copper were comparable with the lowest values obtained in the mesocosms. The lowest chronic NOEC determined for DCA using the laboratory tests was approximately 200 times higher than the lowest NOEC in the mesocosms.

Aquatic toxicity testing of sparingly soluble, volatile, and unstable substances and interpretation and use of data. Task Force of the European Centre for Ecotoxicology and Toxicology of Chemicals.

Aquatic toxicity tests were originally designed for individual compounds that are soluble and stable in water. For sparingly soluble substances that are not toxic at the solubility limit, the issue is whether tests should be performed with insoluble test substance present. Based on a literature evaluation of the physiology of uptake, it was concluded that only the dissolved fraction is available for uptake and that the insoluble test substance may introduce artifacts that aggravate data interpretation. Therefore, toxicity tests should be conducted only up to the solubility limit. Testing of volatile, unstable, or adsorptive substances is complicated by the ability to keep exposure concentrations relatively constant. For these, appropriate test protocols including adequate design of the dosing systems must be employed. For test medium preparation, physical methods and, where necessary, use of low concentrations of certain solvents are recommended to support handling and speed of dissolution. However, recommendation is made against the use of dispersants. Water-accommodated fractions are recommended as one approach for dosing multicomponent substances. Interpretation of observed effects depends on appropriate test medium preparation, correct measurement and expression of exposure levels, and differentiation of true toxicity from indirect physical effects of the substance, or the toxicity of impurities.

A differential PCR assay for the detection of c-erbB 2 amplification used in a prospective study of breast cancer.

AIMS: To establish a robust differential polymerase chain reaction (PCR) assay for the detection of c-erbB 2 amplification in breast cancer that can be used in a routine pathology laboratory. Once established, the assay was used in a prospective study of breast tumours to investigate the relation between c-erbB 2 amplification and both recognised prognostic features and short term clinical outcome. METHODS: The differential PCR was used for the co-amplification of c-erbB 2 and a reference gene from 48 tumour DNA samples and control DNA samples. The ratio of the two genes was determined by image analysis of the PCR products electrophoresed on a highly resolving agarose gel. RESULTS: The differential PCR assay was shown to be accurate and reproducible using the conditions outlined. Twenty six per cent of the breast cancer patients were shown to have c-erbB 2 amplification in their tumour biopsies. Twenty eight per cent of the patients died of their disease or had disease recurrence during the follow up period and 73% of these patients had amplification of c-erbB 2. CONCLUSIONS: A significant association was found between c-erbB 2 amplification and early disease recurrence. This assay could be used to provide a marker for poor prognosis in breast cancer.

Cyclin D1 amplification and expression in human breast carcinoma: correlation with histological prognostic markers and oestrogen receptor expression.

Aims-To study the amplification of the Cyclin D1 gene (CCND1) in human breast carcinoma; to relate this to Cyclin D1 protein expression; to relate these parameters to recognised pathological prognostic factors, including oestrogen receptor (ER) status.Methods-DNA extracted from frozen sections of breast tumours (n = 36) was used for Southern blotting. Probes for CCND1, c-myc and the immunoglobulin heavy chain locus (IgH) were hybridised to tumour DNA. Immunocytochemical expression of Cyclin D1 protein and ER was studied in paraffin wax sections from the same tumours.Results-Amplification of CCND1 was observed in 11% (four of 36) of tumours studied. Over expression of Cyclin D1 protein was observed in 73% (30/41) of tumours. There was no correlation between recognised histological prognostic markers and either gene amplification or expression. However, a weak association was seen between Cyclin D1 expression and ER status.Conclusions-A disparity exists between locus amplification and over expression of Cyclin D1, suggesting the existence of another mechanism for raised protein expression. No significant correlation was detected between either Cyclin D1 amplification or over expression and established prognostic markers.

Hairy polyp of the tonsil.

Hairy polyps or dermoids of the oro- and naso-pharynx are benign lesions containing elements of both ectodermal and mesodermal origin. We report a case of a hairy polyp arising from the tonsil in a three-week-old infant. This presented as an intermittent swelling in the mouth, which was successfully removed under general anaesthesia. To our knowledge this is only the third case of a hairy polyp arising at this site to be reported. We discuss the terminology applied to these lesions and review the literature.

The prognostic significance of caffeine half-life in saliva in children with chronic liver disease.

To evaluate its clinical value, the half-life of caffeine (1,3,7-trimethylxanthine) in saliva (SCT) after 3 mg/kg-1 oral caffeine was measured in 53 children with chronic liver disease (mean age, 4.41 years) and 48 control children (mean age, 6.26 years) in five samples over 24 h and compared with parameters of liver function and outcome. Sensitivity was 60.3% and specificity 97% of SCT for diagnosis of chronic liver disease. The correlation of SCT with serum albumin (ALB) was -0.52 (p < 0.001), total bilirubin (SBR) was 0.585 (p < 0.001), prolonged prothrombin time (PT) was 0.387 (p = 0.004), and aspartate aminotransferase (AST) was 0.538 (p = 0.001). The correlation of SCT with a clinical score of liver dysfunction calculated from the presence of features of hepatic decompensation was 0.627 (p < 0.001) and with Malatack's paediatric prognostic score was 0.505 (p < 0.001). Serial SCT and liver function tests were performed on 53 patients on 127 occasions during a mean follow-up of 361 days (range, 4-709). Of this group, 18 were listed for liver transplantation. Predictive values of outcome by analysis of variance expressed as ratio of mean squares were SBR, 34.1 (p < 0.001); log10 SCT, 20.6 (p < 0.001); ALB, 5.2 (p < 0.05); PT, 1.2 (NS). SCT correlated with clinical and biochemical parameters of severity of liver disease, but SBR was a better predictor of listing for liver transplantation in this group of paediatric patients.

Low plasma ascorbate levels in patients with type 2 diabetes mellitus consuming adequate dietary vitamin C.

Low ascorbate concentrations in diabetes may be secondary to inadequate dietary vitamin C intake or may relate to the varied metabolic roles of the vitamin. To determine whether inadequate dietary intake is a factor we calculated daily vitamin C intakes using both a vitamin C questionnaire and a 4-day food diary in a group of 30 patients with Type 2 diabetes (mean age 68.8 +/- 6.9 yr, 17M/13F) and in 30 community controls (mean age 68.0 +/- 5.5 yr, 12M/18F)). Measures of plasma glucose, serum fructosamine, and plasma ascorbic and dehydroascorbic acid were obtained from 20 subjects in each group. There was no significant difference in daily vitamin C intake between the two groups using both methods: food diary, 61.4 +/- 28.3 (patients) vs 69.5 +/- 33.4 (controls) mg; questionnaire, 54.0 +/- 28.9 (patients) vs 65.0 +/- 30.9 (controls) mg. Vitamin C intake derived from both methods was significantly correlated (p < 0.001). Plasma ascorbate (30.4 +/- 19.1 mumol l-1) and dehydroascorbate (27.6 +/- 6.4 mumol l-1) levels were significantly lower in patients vs in controls (68.8 +/- 36.0 and 31.8 +/- 4.8 mumol l-1, respectively), p < 0.0001 and p < 0.01. Plasma ascorbate levels were significantly correlated with vitamin C intake derived from the food diary (p < 0.01) and questionnaire (p < 0.01) methods in the diabetic group only. Low ascorbate levels in diabetes appears to be a consequence of the disease itself and not due to inadequate dietary intake of vitamin C. A short vitamin C questionnaire is a convenient and reliable estimate of vitamin C intake.(ABSTRACT TRUNCATED AT 250 WORDS)

A double-blind, placebo-controlled parallel trial of vitamin C treatment in elderly patients with hypertension.

We have investigated the effect on blood pressure of treatment with vitamin C (an antioxidant and free radical scavenger) in patients with both systolic and essential hypertension. Following a 2-week run-in phase, two age- and sex-matched groups of untreated hypertensive subjects were randomised in a double-blind study to receive 6 weeks' oral treatment with either vitamin C, 250 mg twice daily (n = 22; 8M/14F, mean age 73.7 +/- 4.9 years) or placebo, one capsule twice daily (n = 26; 10M/16F, mean age 73.8 +/- 5.3 years). Blood pressure was measured in the sitting position using a random zero sphygmomanometer on three occasions during the run-in phase, and again at 2, 4 and 6 weeks after commencing treatment. Venous blood samples for measurement of plasma ascorbic acid (AA) and lipid peroxides (LP) were measured in all subjects at baseline and at 4 and 6 weeks after the start of vitamin C or placebo treatment. During the study period, significant falls in both systolic (vitamin C group, mean change -10.3 (95% CI 0.7-20.0) mm Hg, p = 0.05) and diastolic (vitamin C group, mean change -5.9 (95% CI 0.2-11.5) mm Hg, p = 0.03; placebo group, mean change -4.7 (95% CI 0.3-9.1) mm Hg, p = 0.05) blood pressure occurred. However, no statistical difference between the effects of either treatment on blood pressure was observed. At baseline, AA concentrations were lower in the vitamin C-treated group compared with the placebo group (44.6 +/- 2.4 vs. 57.7 +/- 4.2 mumol/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

The IC50: an exactly defined measure of antibiotic sensitivity.

The concentration of gentamicin that inhibits the growth of half of an inoculum of Pseudomonas aeruginosa (IC50) was estimated by doing viable bacterial counts with varying concentrations of gentamicin and fitting a probit inhibition curve to the results. This is a more precisely defined measure than the MIC and its standard error is readily calculable.