Publications
87 results found
Chataway J, Porter B, Riazi A, et al., 2006, Home versus outpatient administration of intravenous steroids for multiple-sclerosis relapses: a randomised controlled trial., Lancet Neurol, Vol: 5, Pages: 565-571, ISSN: 1474-4422
BACKGROUND: Intravenous steroids are routinely used to treat disabling relapses in multiple sclerosis, and can be administered in an outpatient or home setting. We developed a rating scale that allowed us to compare the two strategies formally in a trial setting. METHODS: Patients who had a clinically significant multiple-sclerosis relapse within 4 weeks of onset were randomly assigned administration of a 3-day regimen of intravenous methylprednisolone either in an outpatient clinic (n=69) or at home (n=69). The MS relapse management scale (MSRMS) was developed to measure patients' experiences of relapse management as the primary outcome. Efficacy of the two treatment modalities was compared in terms of traditional measures and economic cost. A cost-minimisation analysis was also done. Analysis was by intention to treat. FINDINGS: Of 149 eligible patients, 138 consented to participate in the trial and were randomly assigned to a treatment group. Coordination of care was significantly better in the home-treatment group (median score 4.5 [IQR 3.0-11.4]) than in the hospital-treatment group (12.1 [3.0-18.6]; p=0.024). The other dimensions of the MSRMS did not differ between groups (p>0.10). Administration of steroids was equally safe and effective in either location, and cost was either the same or cheaper when delivered at home than when delivered in hospital. INTERPRETATION: Treatment of relapses in multiple sclerosis with intravenous steroids can be effectively and safely administered at home, from both patient and economic perspectives. Moreover, the trial indicates the importance of explicit and valid outcome measures of all aspects of service delivery when making decisions about health policy. This finding has implications for complex service delivery care models for long-term diseases.
Barnes TRE, Mutsatsa SH, Hutton SB, et al., 2006, Comorbid substance use and age at onset of schizophrenia, BRITISH JOURNAL OF PSYCHIATRY, Vol: 188, Pages: 237-242, ISSN: 0007-1250
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- Citations: 187
Williams DR, de Silva R, Paviour DC, et al., 2005, Characteristics of two distinct clinical phenotypes in pathologically proven progressive supranuclear palsy: Richardson's syndrome and PSP-parkinsonism, BRAIN, Vol: 128, Pages: 1247-1258, ISSN: 0006-8950
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- Citations: 520
Barker GJ, Schreiber WG, Gass A, et al., 2005, A standardised method for measuring magnetisation transfer ratio on MR imagers from different manufacturers--the EuroMT sequence., MAGMA, Vol: 18, Pages: 76-80, ISSN: 0968-5243
Magnetisation transfer ratio (MTR) is increasingly used to evaluate neurological disorders, especially those involving demyelination. It shows promise as a surrogate marker of disease progression in treatment trials in multiple sclerosis (MS) but the value measured is highly dependent on pulse sequence parameters, making it hard to include the technique in large multi-centre clinical trials. The variations can be reduced by a normalisation procedure based on the flip angle and timing of the presaturation pulse, but correction for parameters such as saturation pulse shape, amplitude, duration and offset frequency remains problematic. We have defined a standard pulse sequence, to include a standard presaturation pulse and set of parameters, which can be implemented on scanners from both General Electric and Siemens, and has also been used on Phillips scanners. To validate the sequence and parameters, six European centres measured MTR in the frontal white matter of normal volunteers. It was possible to measure MTR values in controls which were consistent to within approximately +/-2.5 percentage units across sites. This degree of precision may be adequate in many situations. The remaining differences between sites and manufacturers are probably caused by B1 errors.
Whitwell JL, Sampson EL, Watt HC, et al., 2005, A volumetric magnetic resonance imaging study of the amygdala in frontotemporal lobar degeneration and Alzheimer's disease, DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, Vol: 20, Pages: 238-244, ISSN: 1420-8008
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- Citations: 42
Godbolt AK, Cipolotti L, Watt H, et al., 2004, The natural history of Alzheimer disease: a longitudinal presymptomatic and symptomatic study of a familial cohort., Arch Neurol, Vol: 61, Pages: 1743-1748, ISSN: 0003-9942
BACKGROUND: Knowledge of the evolution of cognitive deficits in Alzheimer disease is important for our understanding of disease progression. Previous reports, however, have either lacked detail or have not covered the presymptomatic stages. OBJECTIVE: To delineate the onset and progression of clinical and neuropsychological abnormalities in familial Alzheimer disease. METHODS: Nineteen subjects with familial Alzheimer disease underwent serial clinical and neuropsychological assessments. Eight of these had undergone presymptomatic assessments. The follow-up period was 1 to 10 years (mean, 5 years). The relative timing of the occurrence of 3 markers of disease onset and progression (onset of symptoms, Mini-Mental State Examination score < or = 24, and impaired scores on a range of neuropsychological tests) were compared using the binomial exact test. RESULTS: Neurological abnormalities were not prominent, although myoclonus appeared early in some. Mini-Mental State Examination score was not sensitive to early disease. Memory and general intelligence deficits appeared at an earlier stage, in some patients when presymptomatic. Perceptual, naming, and especially spelling skills were preserved to a late stage. CONCLUSION: Familial Alzheimer disease may have a long prodromal phase of several years with subtle deficits initially of general intelligence and memory, while spelling, naming, and perception are relatively preserved until a late stage.
Wright C, Catty J, Watt H, et al., 2004, A systematic review of home treatment services--classification and sustainability., Soc Psychiatry Psychiatr Epidemiol, Vol: 39, Pages: 789-796, ISSN: 0933-7954
BACKGROUND: In view of the plethora of different community-based mental health services, there is a clear need for a classification based on service components rather than labels. Moreover, the sustainability of experimental services beyond their research studies is rarely reported. METHODS: As part of a systematic review of home treatment for mental health problems, authors of all included studies were followed up for data on service components and sustainability. Associations between components were explored. RESULTS: There was evidence of a core group of components co-occurring in home treatment services: regularly visiting at home, taking responsibility for health and social care, having smaller caseloads, multidisciplinary teams, integrated psychiatrists and a high proportion of contacts at home. Fifty-four per cent of services no longer existed, of which almost half had ended by the study's publication date. There was a significant association between sustainability and the study's hospitalisation outcome. CONCLUSIONS: Some of the related service components presented here were associated with reducing hospitalisation. This group cannot, however, be used to provide a new taxonomy of services. It is imperative that future studies prospectively record and report service components to enable better classification. It is of concern that policy is currently predicated on research findings regardless of whether or not the experimental service was sustainable.
Werring DJ, Frazer DW, Coward LJ, et al., 2004, Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI., Brain, Vol: 127, Pages: 2265-2275
Gradient echo T2*-weighted MRI has high sensitivity in detecting cerebral microbleeds, which appear as small dot-like hypointense lesions. Microbleeds are strongly associated with intracerebral haemorrhage, hypertension, lacunar stroke and ischaemic small vessel disease, and have generated interest as a marker of bleeding-prone microangiopathy. Microbleeds have generally been considered to be clinically silent; however, since they are located in widespread cortical and basal ganglia regions and are histologically characterized by tissue damage, we hypothesized that they would cause cognitive dysfunction. We therefore studied patients with microbleeds (n = 25) and a non-microbleed control group (n = 30) matched for age, gender and intelligence quotient. To avoid the confounding effects of coexisting cerebrovascular disease, the groups were also matched for the extent of MRI-visible white matter changes of presumed ischaemic origin, location of cortical strokes, and for the proportion of patients with different stroke subtypes (including lacunar stroke). A battery of neuropsychological tests was used to assess current intellectual function, verbal and visual memory, naming and perceptual skills, speed and attention and executive function. Microbleeds were most common in the basal ganglia but were also found in frontal, parieto-occipital, temporal and infratentorial regions. There was a striking difference between the groups in the prevalence of executive dysfunction, which was present in 60% of microbleed patients compared with 30% of non-microbleed patients (P = 0.03). Logistic regression confirmed that microbleeds (but not white matter changes) were an independent predictor of executive impairment (adjusted odds ratio = 1.32, 95% confidence interval 1.01-1.70, P = 0.04). Patients with executive dysfunction had more microbleeds in the frontal region (mean count 1.54 versus 0.03; P = 0.002) and in the basal ganglia (mean 1.17 versus 0.32; P = 0.048). There was a modes
McCabe DJH, Harrison P, Mackie IJ, et al., 2004, Platelet degranulation and monocyte-platelet complex formation are increased in the acute and convalescent phases after ischaemic stroke or transient ischaemic attack., Br J Haematol, Vol: 125, Pages: 777-787, ISSN: 0007-1048
Flow cytometric studies suggest that platelets are activated in ischaemic stroke or transient ischaemic attack (TIA). However, few studies have measured circulating leucocyte-platelet complexes in this patient population. Whole blood flow cytometry was used to quantify the expression of CD62P-, CD63-, and PAC1-binding, and the percentages of leucocyte-platelet complexes in acute (1-27 d, n = 79) and convalescent (79-725 d, n = 70) ischaemic cerebrovascular disease (CVD) patients compared with controls without CVD (n = 27). We performed a full blood count, and measured plasma levels of soluble P-selectin, soluble E-selectin, and von Willebrand factor antigen (VWF:Ag) as additional markers of platelet and/or endothelial cell activation. The median percentage CD62P expression and the median percentage monocyte-platelet complexes were higher in both acute and convalescent CVD patients than controls (P </= 0.02). The mean white cell count and mean VWF:Ag levels were significantly elevated in the acute and convalescent phases after ischaemic stroke or TIA (P </= 0.02). Otherwise, there was no significant increase in any other marker of platelet or endothelial activation in CVD patients. There was a positive correlation between the percentage expression of CD62P and the percentages of both neutrophil-platelet and monocyte-platelet complexes in the acute phase, and the percentages of all leucocyte-platelet complexes in the convalescent phase after ischaemic CVD. This study provides evidence for ongoing excessive platelet and/or endothelial activation in ischaemic CVD patients despite treatment with antithrombotic therapy.
Khan NL, Katzenschlager R, Watt H, et al., 2004, Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease., Neurology, Vol: 62, Pages: 1224-1226
The authors studied whether olfactory dysfunction is present in parkin disease using the University of Pennsylvania Smell Identification Test (UPSIT). The mean UPSIT score in parkin patients was 27.3 (95% CI 24.4 to 30.2). This did not differ from the normal group mean of 29.4 (95% CI 28.0 to 30.7; p = 0.22) but was higher than the Parkinson disease group (mean 14.3; 95% CI 12.2 to 19.5; p < 0.0001) and the parkin-negative group (mean 17.1; 95% CI 14.8 to 16.3; p < 0.0001) values. Parkin disease may be a distinct and separate entity from Parkinson disease.
Whitwell JL, Schott JM, Watt HC, et al., 2004, Correcting brain volumes for total intracranial volume: Applications in serial studies of Alzheimer's disease, 2nd Meeting of the Alzheimers Imaging Consortium, Publisher: ELSEVIER SCIENCE INC, Pages: 270-270, ISSN: 0197-4580
Chan D, Janssen JC, Whitwell JL, et al., 2003, Change in rates of cerebral atrophy over time in early-onset Alzheimer's disease: longitudinal MRI study, LANCET, Vol: 362, Pages: 1121-1122, ISSN: 0140-6736
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- Citations: 154
Petzold A, Jenkins R, Watt HC, et al., 2003, Cerebrospinal fluid S100B correlates with brain atrophy in Alzheimer's disease, NEUROSCIENCE LETTERS, Vol: 336, Pages: 167-170, ISSN: 0304-3940
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- Citations: 88
Wiseman OJ, Brady CM, Hussain IF, et al., 2002, The ultrastructure of bladder lamina propria nerves in healthy subjects and patients with detrusor hyperreflexia., J Urol, Vol: 168, Pages: 2040-2045, ISSN: 0022-5347
PURPOSE: Detrusor hyperreflexia is a common finding in patients with neurological disease involving the spinal cord. In animal models it has been attributed to an emergent reflex mediated mostly by unmyelinated C-fibers. We describe and measure ultrastructural features of these nerves in the lamina propria in healthy subjects and patients with detrusor hyperreflexia. MATERIALS AND METHODS: Flexible cystoscopic bladder biopsies were obtained from 51 patients (8 controls, 8 with tropical spastic paraparesis, 23 with multiple sclerosis and 12 with spinal cord disease). Electron micrographs were obtained of every nerve profile seen in the midpoint of the biopsy specimen, and in each nerve profile a number of variables were measured and recorded. RESULTS: The mean nerve profile diameter was greater in patients with tropical spastic paraparesis (mean 2.19 microm.) compared to controls (1.59 microm.) and patients with multiple sclerosis (1.55 microm.) (p <0.001). We observed a sparse urothelial innervation by naked axonal varicosities but similar bare varicosities were more frequent in the superficial layer of the lamina propria. In deeper layers close membrane contacts between axonal varicosities and cells with cytological characteristics of myofibroblasts were seen. CONCLUSIONS: We described and measured ultrastructural characteristics of human bladder lamina propria nerves. The mean profile diameter is larger in patients with tropical spastic paraparesis compared to controls and patients with multiple sclerosis. This study provides a baseline to which other bladder disorders can be compared and may allow the effect of intravesical treatments on these nerves to be assessed. Some possible functional aspects of observed structural interrelationships are presented.
Burns T, Catty J, Watt H, et al., 2002, International differences in home treatment for mental health problems. Results of a systematic review., Br J Psychiatry, Vol: 181, Pages: 375-382, ISSN: 0007-1250
BACKGROUND: It is perceived that North American home treatment studies reveal greater success in reducing days in hospital than do European studies. There are difficulties in extrapolating findings internationally. AIMS: We aimed to determine whether North American studies find greater reductions in days in hospital and whether experimental service patients in North American studies spend less time in hospital. METHOD: The results of a systematic review were analysed with respect to study location. Service components ascertained through follow-up were utilised to interpret the meta-analyses conducted. RESULTS: Most of the 91 studies found were from the USA and UK. North American studies found a difference of one hospital day (per patient per month) more than European studies but there was no difference in experimental data between the two locations. CONCLUSIONS: North American studies demonstrate greater differences in days in hospital but patients in their experimental services seem to spend no fewer days in hospital, implying a disparity in control services.
Catty J, Burns T, Knapp M, et al., 2002, Home treatment for mental health problems: a systematic review., Psychol Med, Vol: 32, Pages: 383-401, ISSN: 0033-2917
BACKGROUND: Concerns have been raised about the scope and generalizability of much community mental health research. In particular, both experimental and control services are poorly characterized. METHODS: To review the effectiveness of 'home treatment' for mental health problems in terms of hospitalization, we conducted a systematic review, using Cochrane methodology but with a wider remit. Non-randomized studies were included in response to concerns about RCTs' generalizability. All authors were followed up for data on service components. 'Home treatment' was defined broadly for the purposes of the literature search, but included studies were then assessed against service components specifically focused on delivering treatment at home. The study tested components and other features for associations with days in hospital, as well as conducting a conventional meta-analysis of data on days in hospital. RESULTS: We found 91 studies, 18 comparing home to in-patient treatment. Sixty per cent of authors responded to follow-up. The vast majority of the services studied had a 'home treatment function' and regularly visited patients at home. The heterogeneity of control services made meta-analysis problematical as did the limited availability of data. There was some evidence that 'regular' home visiting and combined responsibility for health and social care were associated with reduced hospitalization. The inclusion of non-randomized studies rarely affected the findings. CONCLUSIONS: Evidence concerning the effectiveness of home treatment remains inconclusive. A centrally coordinated research strategy is recommended, with attention to study design. Experimental and control service components should be prospectively recorded and reported to enable meaningful analysis.
Whitwell JL, Crum WR, Watt HC, et al., 2001, Normalization of cerebral volumes by use of intracranial volume: Implications for longitudinal quantitative MR imaging, Publisher: AMER SOC NEURORADIOLOGY, Pages: 1483-1489, ISSN: 0195-6108
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- Citations: 287
Burns T, Knapp M, Catty J, et al., 2001, Home treatment for mental health problems: a systematic review., Health Technol Assess, Vol: 5, Pages: 1-139, ISSN: 1366-5278
This review investigates the effectiveness of 'home treatment' for mental health problems in terms of hospitalisation and cost-effectiveness. For the purposes of this review, 'home treatment' is defined as a service that enables the patient to be treated outside hospital as far as possible and remain in their usual place of residence. METHODS - SYSTEMATIC LITERATURE SEARCH: 'Home treatment' excluded studies focused on day, residential and foster care. The review was based on Cochrane methodology, but non-randomised studies were included if they compared two services; these were only analysed if they provided evidence of the groups' baseline clinical comparability. METHODS - REVIEW OF ECONOMIC EVALUATIONS: Economic evaluations among the studies found were reviewed against established criteria. METHODS - IDENTIFICATION OF SERVICE COMPONENTS: A three-round Delphi exercise ascertained the degree of consensus among expert psychiatrists concerning the important components of community-based services that enable them to treat patients outside hospital. The identified components were used to construct the follow-up questionnaire. METHODS - FOLLOW-UP OF AUTHORS: As a supplement to the information available in the papers, authors of all the studies were followed up for data on service components, sustainability of programmes and service utilisation. METHODS - DATA ANALYSIS: The outcome measure was mean days in hospital per patient per month over the follow-up period. (1) Comparative analysis - compared experimental to control services. It analysed all studies with available data, divided into 'inpatient-control' and 'community-control' studies, and tested for associations between service components and difference in hospital days. (2) Experimental services analysis - analysed only experimental service data and tested for associations between service components and hospital days. RESULTS - SYSTEMATIC LITERATURE SEARCH: A total of 91 studies were found, conducted over a 30-year
Wald NJ, Watt HC, George L, et al., 2000, Adding free to total prostate-specific antigen levels in trials of prostate cancer screening., British Journal of Cancer, Vol: 82, Pages: 731-736, ISSN: 0007-0920
We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to alpha-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials.
Wald NJ, Watt HC, Hackshaw AK, 1999, Integrated screening for Down's syndrome based on tests performed during the first and second trimesters., N Engl J Med, Vol: 341, Pages: 461-467, ISSN: 0028-4793
BACKGROUND: Both first-trimester screening and second-trimester screening for Down's syndrome are effective means of selecting women for chorionic-villus sampling or amniocentesis, but there is uncertainty about which screening method should be used in practice. We propose a new screening method in which measurements obtained during both trimesters are integrated to provide a single estimate of a woman's risk of having a pregnancy affected by Down's syndrome. METHODS: We used data from published studies of various screening methods employed during the first and second trimesters. The first-trimester screening consisted of measurement of serum pregnancy-associated plasma protein A in 77 pregnancies affected by Down's syndrome and 383 unaffected pregnancies and measurements of nuchal translucency obtained by ultrasonography in 326 affected and 95,476 unaffected pregnancies. The second-trimester tests were various combinations of measurements of serum alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin A in 77 affected and 385 unaffected pregnancies. RESULTS: When we used a risk of 1 in 120 or greater as the cutoff to define a positive result on the integrated screening test, the rate of detection of Down's syndrome was 85 percent, with a false positive rate of 0.9 percent. To achieve the same rate of detection, current screening tests would have higher false positive rates (5 to 22 percent). If the integrated test were to replace the triple test (measurements of serum alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin), currently used with a 5 percent false positive rate, for screening during the second trimester, the detection rate would be higher 85 percent vs. 69 percent), with a reduction of four fifths in the number of invasive diagnostic procedures and consequent losses of normal fetuses. CONCLUSIONS: The integrated test detects more cases of Down's syndrome with a much lower false positive rate than the best
Wald NJ, Watt HC, Norgaard-Pedersen B, et al., 1999, SP1 in pregnancies with Down syndrome in the first trimester of pregnancy. International Prenatal Screening Research Group., Prenat Diagn, Vol: 19, Pages: 517-520, ISSN: 0197-3851
We conducted a study to determine the value of serum pregnancy-specific beta-1-glycoprotein (Schwangerschafts protein 1, SP1) as an antenatal screening test for Down syndrome in the first trimester. Serum samples collected from women at 8 to 14 weeks of pregnancy, immediately prior to having a chorionic villus sampling procedure on account of advanced maternal age, were retrieved from 96 women with Down syndrome pregnancies (cases) and from 480 women with unaffected pregnancies (controls). Cases and controls were ascertained at 21 obstetric centres in nine countries. Each case was matched with five controls for maternal age (same five-year age groups), duration of storage of the serum sample (same calendar year) and gestational age (usually the same week of pregnancy). The levels of SP1 were lower in pregnancies associated with Down syndrome: the median level was 0.86 multiples of the median level in the controls (95 per cent confidence interval 0.76 to 0.97). This difference, though statistically significant, was not large enough for SP1 to be a useful marker in screening, at least from 10 weeks onwards where most of our data lie.
Morris JK, Wald NJ, Watt HC, 1999, Fetal loss in Down syndrome pregnancies., Prenat Diagn, Vol: 19, Pages: 142-145, ISSN: 0197-3851
It is recognized that pregnancies with Down syndrome are liable to end in spontaneous fetal loss. It is important to determine the magnitude of this effect so that it can be taken into account when assessing the results of antenatal screening programmes for Down syndrome. Failure to do so will tend to overestimate the detection rate in intervention studies in which the screening results are used to identify women for a diagnostic test and the offer of a termination of pregnancy if indicated. We present new data on the spontaneous fetal loss in Down syndrome pregnancies from the National Down Syndrome Cytogenetic Register (1989-1996). We compare our results with published results of other studies on the subject to obtain a summary estimate. We exclude one study from the meta analysis due to incorrect methodology resulting in an overestimate of fetal loss. Based on the combined data (i) between the time of chorionic villus sampling and term an estimated 43 per cent (95 per cent CI: 31-54 per cent) of pregnancies ended in a miscarriage or still birth, (ii) between the time of amniocentesis and term an estimated 23 per cent (95 per cent CI: 19 28 per cent) of pregnancies ended in a miscarriage or still birth, and (iii) 12 per cent (95 per cent CI: 2-23 per cent) of births were stillborn or resulted in a neonatal death.
Wald NJ, Watt HC, 1999, The target plot: a new way of displaying the performance of a screening test., J Med Screen, Vol: 6, Pages: 195-199, ISSN: 0969-1413
OBJECTIVES: To produce a graphical method to represent the performance of a screening test that illustrates the prevalence of the disorder being screened for, as well as its discriminatory potential. CONCEPT: A target plot was constructed in which the risk of the disorder is represented by a series of concentric circles of constant risk (isorisks) equivalent to specified false positive rates, with the highest risk in the centre and lower risks spreading outwards towards the circumference. Dots were drawn to represent cases of the disorder; these were of a size such that their total area as a proportion of the area of the whole target plot equalled the prevalence of the disorder in the screened population. The discriminatory power of the test was seen as the clustering of dots around the centre or bull's eye of the target. The detection rate could be estimated as the proportion of dots which fell within the isorisk corresponding to a specified false positive rate. APPLICATION: The target plot was applied to second trimester antenatal screening for Down's syndrome using different combinations of screening markers, and also to screening for ischaemic heart disease using protein components of cholesterol (apolipoproteins A I and B and Lp(a) lipoprotein), systolic blood pressure, and smoking status. DISCUSSION: The efficacy of the different methods of screening for Down's syndrome is readily apparent using the target plot, as is the poorer performance of screening for ischaemic heart disease. CONCLUSIONS: The target plot is a simple and quantitative way of displaying the performance of a screening test that may be useful in teaching and educational material.
Wald NJ, Watt HC, Law MR, et al., 1998, Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention., Arch Intern Med, Vol: 158, Pages: 862-867, ISSN: 0003-9926
BACKGROUND: Results from prospective studies of serum homocysteine levels and ischemic heart disease (IHD) are inconclusive. We carried out a further prospective study to help clarify the position. METHODS: In the British United Provident Association (BUPA) prospective study of 21,520 men aged 35 to 64 years, we measured homocysteine levels in stored serum samples and analyzed data from 229 men without a history of IHD at study entry who subsequently died of IHD and 1126 age-matched control subjects (nested case-control design). RESULTS: Serum homocysteine levels were significantly higher in men who died of IHD than in men who did not (mean, 13.1 vs 11.8 micromol/L; P<.001). The risk of IHD among men in the highest quartile of serum homocysteine levels was 3.7 times (or 2.9 times after adjusting for other risk factors) the risk among men in the lowest quartile (95% confidence interval [CI], 1.8-4.7). There was a continuous dose-response relationship, with risk increasing by 41% (95% CI, 20%-65%) for each 5-micromol/L increase in the serum homocysteine level. After adjustment for apolipoprotein B levels and blood pressure, this estimate was 33% (95% CI, 22%-59%). In a meta-analysis of the retrospective studies of homocysteine level and myocardial infarction, the age-adjusted association was stronger: an 84% (95% CI, 52%-123%) increase in risk for a 5-micromol/L increase in the homocysteine level, possibly because the participants were younger; the relationship between serum homocysteine level and IHD seems to be stronger in younger persons than in older persons. CONCLUSIONS: Our positive results help resolve the uncertainty that resulted from previous prospective studies. The epidemiological, genetic, and animal evidence together indicate that the association between serum homocysteine level and IHD is likely to be causal. A general increase in consumption of the vitamin folic acid (which reduces serum homocysteine levels) would, therefore, be expected to reduce m
Wald NJ, Watt HC, Haddow JE, et al., 1998, Screening for Down syndrome at 14 weeks of pregnancy., Prenat Diagn, Vol: 18, Pages: 291-293, ISSN: 0197-3851
To investigate whether statistical parameters used in Down syndrome screening between 15 and 22 weeks of pregnancy can be used at 14 weeks, we assayed alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, and inhibin-A in 16 pregnancies with Down syndrome in the 14th week of pregnancy and expressed values in multiples of the normal median. The median and standard deviation values for these 16 pregnancies were not materially different from those published for 15-22 weeks. It is reasonable, therefore, to offer Down syndrome screening using these markers starting at 14 completed weeks of pregnancy instead of 15 weeks. It needs to be recognized, however, that serum AFP measurement for neural tube defect screening is less effective at this time than between 16 and 18 weeks of pregnancy.
Law MR, Morris JK, Watt HC, et al., 1997, The dose-response relationship between cigarette consumption, biochemical markers and risk of lung cancer., British Journal of Cancer, Vol: 75, Pages: 1690-1693, ISSN: 0007-0920
The relationship between the number of cigarettes smoked per day and the incidence of lung cancer is linear but, from the multistage model of carcinogenesis, it should be quadratic (upwards curving). We investigated this anomaly in a study of 11,403 male never smokers and current smokers in whom carboxyhaemoglobin (COHb) was measured in all and serum cotinine in 1175. The relationship between the biochemical markers and the reported number of cigarettes per day was approximately linear up to 20 cigarettes per day as expected. But above 20 cigarettes per day the marker levels increased less steeply and were 35% lower than expected in men who smoked more than 40 cigarettes per day. Less smoke is inhaled from each cigarette by men with high daily cigarette consumption than by men with lower consumption. Allowance for this transforms the observed linear dose-response relationship into one consistent with the expected quadratic relationship. The anomaly is explained by the observation that heavier smokers inhale less smoke from each cigarette.
Huang T, Watt HC, Wald NJ, et al., 1997, Reliability of statistics on Down's syndrome notifications., J Med Screen, Vol: 4, Pages: 95-97, ISSN: 0969-1413
OBJECTIVES: To evaluate the completeness of notifications of Down's syndrome live births and terminations to the Office for National Statistics (ONS) using data from the National Down Syndrome Cytogenetic Register (NDSCR). To examine the agreement of observed birth prevalence of Down's syndrome with the expected birth prevalence derived from published maternal age specific rates. METHODS: The number of live births (adjusted to allow for the estimated underascertainment) and the number of terminations due to fetal Down's syndrome from NDSCR were compared with those figures reported to the ONS. Subsequently, using the NDSCR figures, the live birth prevalence of Down's syndrome that would have occurred in the absence of antenatal diagnosis and selective termination was calculated in England and Wales in the years 1990-1993. These figures were compared with those derived by applying published age specific prevalences to the maternal age distribution in England and Wales. RESULTS: It is estimated that only 48% and 46% respectively of Down's syndrome live births and terminations of pregnancy were notified to ONS between 1990 and 1993. The annual expected birth prevalences of Down's syndrome obtained by applying maternal age specific prevalences to the maternal age distribution were in close agreement with observed rates from NDSCR. CONCLUSIONS: There is considerable underreporting of Down's syndrome births and terminations to ONS. The NDSCR data are more complete and therefore the effects of screening should be monitored using data from this source, or using estimates derived from the age specific rates of Down's syndrome.
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