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Biomedical subjects

L Irwig

Publications and source records attributed to L Irwig.

At least 19 recordsLinked to original sources
PubMed2002

Serological diagnosis of pertussis: evaluation of IgA against whole cell and specific Bordetella pertussis antigens as markers of recent infection.

In Australia, notification of pertussis cases in older children or adults has increased significantly in recent years. In most cases, laboratory diagnosis is based only on a positive serological test for IgA antibody against whole cell Bordetella pertussis. During a 3-month period, 318 consecutive sera submitted for diagnosis of pertussis were tested for IgA antibody against whole cell (WC) sonicated B. pertussis, pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). Results of one or more of these tests were positive in sera from 175 subjects and clinical information was obtained by telephone interview from 90 subjects. Using a clinical case definition as the reference standard, the sensitivities of the four IgA assays were variable but quite low (24-64%), but the specificities were high (93-98%). For diagnosis of pertussis in subjects with a compatible clinical illness, these and other findings support the use of serological testing for IgA antibody.

Adolescent↗
PubMed2002

Cancer screening.

"Screening is the systematic application of a test or inquiry, to identify individuals at sufficient risk of a specific disorder to benefit from further investigation or direct preventive action, among persons who have not sought medical attention on account of symptoms of that disorder."

Adult↗
PubMed2001

Estimating the number needed to treat (NNT) index when the data are subject to error.

The number needed to treat (NNT) index has been proposed as a clinically useful measure to assess the results of randomized trials and other clinical studies. In its usual form, NNT indicates the expected number of patients who must be treated with an experimental therapy in order to prevent one adverse event, compared to the expected event rates under the control therapy. It can be formulated as a function of the proportions of patients who respond to treatment by more than a certain amount, the clinically important difference. We may also wish to evaluate two group studies comparing treatment and control responses, and to consider net benefit from treatment (by also allowing for individuals who deteriorate as well as those who respond positively). In this paper, we investigate the effect on NNT caused by measurement errors in continuous outcome measures. Such errors can lead to bias in the estimated proportions of subjects with clinically important responses, and hence bias the associated values of NNT. General expressions for the bias are derived, and enumerated for typical scenarios. For many situations, reliability of 80 per cent or more in the observations is required to restrict the bias to tolerable levels.

Bias↗
PubMed2001

A comparison of methods to detect publication bias in meta-analysis.

Meta-analyses are subject to bias for many of reasons, including publication bias. Asymmetry in a funnel plot of study size against treatment effect is often used to identify such bias. We compare the performance of three simple methods of testing for bias: the rank correlation method; a simple linear regression of the standardized estimate of treatment effect on the precision of the estimate; and a regression of the treatment effect on sample size. The tests are applied to simulated meta-analyses in the presence and absence of publication bias. Both one-sided and two-sided censoring of studies based on statistical significance was used. The results indicate that none of the tests performs consistently well. Test performance varied with the magnitude of the true treatment effect, distribution of study size and whether a one- or two-tailed significance test was employed. Overall, the power of the tests was low when the number of studies per meta-analysis was close to that often observed in practice. Tests that showed the highest power also had type I error rates higher than the nominal level. Based on the empirical type I error rates, a regression of treatment effect on sample size, weighted by the inverse of the variance of the logit of the pooled proportion (using the marginal total) is the preferred method.

Computer Simulation↗
PubMed2000

Screening for colorectal cancer using the faecal occult blood test, hemoccult.

BACKGROUND: Colorectal cancer is a leading cause of illness and death in the Western world. In Australia, the United Kingdom and the United States, it is the second commonest cancer for women after breast cancer (age-standardised incidence 22-33 per 100,000), and men after prostate or lung cancer (age-standardised incidence 31-47 per 100,000) (Jeffs et al, 1996; Parkin et al, 1992). Just under half of all persons affected will die from their disease (Jeffs et al, 1996; Parkin et al, 1992) The human and financial costs of this disease have prompted considerable research efforts to evaluate the ability of screening tests to detect the cancer at an early curable stage. Tests which have been considered for screening include faecal occult blood tests, sigmoidoscopy and colonoscopy. OBJECTIVES: To determine whether screening for colorectal cancer using the faecal occult blood test, Hemoccult reduces colorectal cancer mortality and to consider the benefits and harms of screening. SEARCH STRATEGY: Published and unpublished data for this review were identified by: * retrieving studies included in a systematic review conducted by some of the authors in 1995, * searches of MEDLINE, Current Contents and the Cochrane Controlled Trials Register, * writing to trial lists. SELECTION CRITERIA: All controlled trials of screening for colorectal cancer using Hemoccult were eligible for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data from the trials were independently extracted by two authors. Data analysis was performed using the group subjects were randomised to ('intention to screen'), whether or not they were ever screened. To estimate the effect of Hemoccult screening on colorectal cancer mortality, we calculated relative risks and risk differences for each trial, and then overall, using fixed and random effects models and tested for heterogeneity of effects. We calculated summary measures of effect including all trials and also for just the randomised controlled trials. We also calculated a summary measure of effect, adjusted for attendance at screening in each trial (not shown in Meta-view). MAIN RESULTS: Meta-analysis of mortality results from the randomised controlled trials shows that those allocated to screening had a reduction in colorectal cancer mortality of 16% (RR 0.84, CI: 0.77-0.93). When adjusted for screening attendance in the individual studies, the mortality reduction is 23% (RR 0.77, CI: 0.57-0.89). Overall, if 10 000 people were offered a biennial Hemoccult screening program and two-thirds attended for at least one Hemoccult test, there would be 8.5 deaths (CI: 3.6-13.5) from colorectal cancer prevented over 10 years. However, the screening program would also result in 2 800 participants having at least one colonoscopy, if screening harms from the Minnesota trial are considered, and there would be 3.4 colonoscopy complications (perforation or haemorrhage). If screening harms from the Gothenburg trial are considered, approximately 600 participants would need at least one sigmoidoscopy and double contrast barium enema, resulting in 1.8 perforations or haemorrhages. REVIEWER'S CONCLUSIONS: Screening benefits include reduction in colorectal cancer mortality, possible reduction in cancer incidence through detection and removal of colorectal adenomas and potentially, treatment of early colorectal cancers may involve less invasive surgery. Harmful effects of screening include the physical complications of colonoscopy, disruption to lifestyle, stress and discomfort of testing and investigations, and the anxiety caused by falsely positive screening tests. Although screening benefits are likely to outweigh harms for populations at increased risk of colorectal cancer, we need more information about the harmful effects of screening, the community's responses to screening and screening costs for different health care systems before widespread screening can be recommended.

Colorectal Neoplasms↗
PubMed2000

Reliability of DMSA for the diagnosis of renal parenchymal abnormality in children.

The objective of this study was to evaluate the variability of technetium-99m dimercaptosuccinic acid (DMSA) scintigraphy interpretation by four nuclear medicine physicians for the diagnosis of renal parenchymal abnormality in children, and to compare variability among three different DMSA methods in clinical use: planar alone, single-photon emission tomography (SPET) alone, and planar with SPET. One hundred consecutive DMSA studies were independently interpreted 3 times by four participating nuclear medicine specialists from different departments and in random order. All scans were classified by the presence or absence of renal parenchymal abnormality using the modified four-level grading system of Goldraich. Indices of agreement were the percentage of agreement and the kappa statistic. Disagreement was analysed using children, kidneys and kidney zones (three zones per kidney). Using patients as the unit of analysis, agreement for planar and planar with SPET methods was 87%-88% (kappa 0.74) for the normal-abnormal scan classification. The corresponding agreement value for the SPET alone method was 78% (kappa 0.56). Similarly, substantial disagreement (disagreement > or = 2 categories) occurred in 2.5% and 1.3% of comparisons between observers for planar alone and planar with SPET, respectively, but in 5.2% of comparisons for SPET alone. These results did not vary appreciably whether interpretation of patients, kidneys or kidney zones was compared. It is concluded that the four experienced nuclear medicine physicians showed substantial agreement in the interpretation of planar alone and planar with SPET DMSA scintigraphic images. Interpretation of SPET DMSA images, without planar images, was significantly more variable than interpretation using the two other methods, disagreement occurring in more than 20% of comparisons. SPET DMSA scintigraphy, when used without planar images, does not provide a firm basis for clinical decision making in the care of children who may have renal damage. There is no apparent benefit of reduced variability from the extra provision of SPET data to nuclear medicine physicians who already have planar images.

Child↗
PubMed2000

How accurate is dimercaptosuccinic acid scintigraphy for the diagnosis of acute pyelonephritis? A meta-analysis of experimental studies.

UNLABELLED: The purpose of this study was to evaluate the performance of dimercaptosuccinic acid (DMSA) scintigraphy in the diagnosis of acute pyelonephritis and to compare the test performance of the standard technique, planar DMSA, with the newly introduced technique, SPECT DMSA. METHODS: All published animal studies in which DMSA scintigraphy was compared with histopathology, the reference standard for acute pyelonephritis, were identified using a comprehensive search strategy with the MEDLINE and EMBASE databases. Test performances of all DMSA methods and SPECT versus planar DMSA were analyzed using summary receiver operating characteristic (sROC) curves. RESULTS: Seven studies were identified, including 2 of SPECT DMSA. Problems in study design or reporting were common, with numerical errors in 4 studies. Overall, at a sensitivity of 86%, specificity was estimated to be 91%. Detection of acute pyelonephritis was at a lower threshold for SPECT than for planar DMSA (sensitivity/specificity values of 97%0/66% compared with 82%/ 97%), and the overall test performance of SPECT was not demonstrably better than that of planar DMSA. When applied to a group of children with a prevalence of renal damage of 40%, this means that 98% of children with abnormal planar DMSA scans will have renal damage, whereas only 65% of those with abnormal SPECT scans will have renal damage. Planar and SPECT DMSA will miss 11% and 3% of children with renal damage, respectively. Out of 100 children in the hypothetical group with 40% experiencing renal damage, SPECT will identify 6 extra true cases of renal damage at the expense of 19 extra false positives, when compared with planar DMSA. CONCLUSION: Published studies of DMSA test performance are few in number and have significant methodologic problems that should be avoided in future studies. DMSA, particularly the planar technique, performs well for the diagnosis of acute pyelonephritis. Using test performance criteria, SPECT DMSA alone has not been shown to be preferable to the established planar method and will result in a small number of true-positives at the expense of a larger number of false-positives.

Acute Disease↗
PubMed2000

Should we use carbohydrate-deficient transferrin instead of gamma-glutamyltransferase for detecting problem drinkers? A systematic review and metaanalysis.

BACKGROUND: Carbohydrate-deficient transferrin (CDT) has been used as a test for excessive alcohol consumption in research, clinical, and medico-legal settings, but there remain conflicting data on its accuracy, with sensitivities ranging from <20% to 100%. We examined evidence of its benefit over a conventional and less expensive test, gamma-glutamyltransferase (GGT), and compared the accuracy of different CDT assay methods. METHODS: We performed a systematic review using summary ROC analysis of 110 studies prior to June 1998 on the use of CDT in the detection of alcohol dependence or hazardous/harmful alcohol use. RESULTS: We identified several potential sources of bias in studies. In studies examining CDT and GGT in the same subjects, subject characteristics were less likely to influence the comparison. In such paired studies, the original Pharmacia CDT assay was significantly more accurate than GGT, but the modified CDTect assay did not perform as well as the original and was not significantly better than GGT. The accuracy of the AXIS %CDT assay was statistically indistinguishable from modified CDTect. Several CDT assay methods appeared promising, in particular, liquid chromatography (chromatofocusing, HPLC, fast protein liquid chromatography) and isoelectric focusing, but there were insufficient paired studies from which to draw firm conclusions. CONCLUSIONS: In studies published before June 1998, the results obtained with commercially available CDT assays were not significantly better than GGT as markers of excessive alcohol use in paired studies. Further high-quality studies comparing CDTect (modified) and other CDT assays with GGT in the same subjects are needed.

Age Factors↗
PubMed1999

Meta-analysis of diagnostic tests with imperfect reference standards.

We present a method to estimate the summary receiver operating characteristic (SROC) curve for combining information on a diagnostic test from several different studies. Unlike previous methods that assume the reference standard to be error free, our approach allows for the possibility of errors in the reference standard, through use of a latent class model. The model provides estimates of the sensitivity and specificity of the diagnostic test and the case prevalence in each study; these parameters can then be used in a meta-analysis, for example, using the regression method proposed by Moses et al., of a measure of test discrimination on a measure of the diagnostic threshold, to fit the SROC. The method is illustrated with an example on Pap smears that shows how adjusting for imperfection in the reference standard typically reduces the scatter of data in the SROC plot, and tends to indicate better performance of the test than otherwise.

Algorithms↗
PubMed1999

Randomized double-blind trial of beta-carotene and vitamin C in women with minor cervical abnormalities.

A double-blind, placebo-controlled, randomized, factorial study using a daily oral administration of 30 mg beta-carotene and/or 500 mg vitamin C was conducted in 141 women with colposcopically and histologically confirmed minor squamous atypia or cervical intra-epithelial neoplasia (CIN) I. Over approximately 2 years of follow-up, 43 lesions regressed to normal and 13 progressed to CIN II. The regression rate was slightly higher, but not significantly so, in those randomized to beta-carotene compared to no beta-carotene (hazard ratio = 1.58, 95% CI: 0.86-2.93, P = 0.14) and slightly lower, but not statistically significant, for those randomized to vitamin C compared to no vitamin C (hazard ratio = 0.65, 95% CI: 0.35-1.21, P = 0.17). In a model with no interaction, the progression rate was slightly higher in those randomized to beta-carotene (hazard ratio = 1.75, 95% CI: 0.57-5.36, P = 0.32) and also in those randomized to vitamin C (hazard ratio = 2.40, 95% CI: 0.74-7.80, P = 0.13). Neither of these were statistically significant. However, there was some evidence of an interaction effect of the two compounds on the progression rate (P = 0.052), with seven of the progressed lesions occurring in those randomized to both vitamins compared to a total of six in the three other groups. The currently available evidence from this and other trials suggests that high doses of these compounds are unlikely to increase the regression or decrease the progression of minor atypia and CIN I.

Adult↗
PubMed1998

Staff attitudes and retention of patients in methadone maintenance programs.

A study was made of the effect of staff commitment to abstinence-oriented policies on retention of patients in methadone maintenance. Staff working in six public methadone programs in Sydney, Australia, were surveyed in 1989 and 1992 using the Abstinence Orientation Scale. The association of the clinics' median Abstinence Orientation scores with the time in treatment of a random sample of their 1988-1989 admissions was summarised using Cox regression. Patients' risk of discharge increased by a factor of three with every one unit increase in the clinics' median Abstinence Orientation scores, (RR 3.4, 95% CI 2.3-5.0). Abstinence-oriented policies were shown to disadvantage ex-prisoners.

Adult↗
PubMed1998

A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, hemoccult.

OBJECTIVE: To review effectiveness of screening for colorectal cancer with faecal occult blood test, Hemoccult, and to consider benefits and harms of screening. DESIGN: Systematic review of trials of Hemoccult screening, with meta-analysis of results from the randomised controlled trials. SUBJECTS: Four randomised controlled trials and two non-randomised trials of about 330 000 and 113 000 people respectively aged >=40 years in five countries. MAIN OUTCOME MEASURES: Meta-analysis of effects of screening on mortality from colorectal cancer. RESULTS: Quality of trial design was generally high, and screening resulted in a favourable shift in the stage distribution of colorectal cancers in the screening groups. Meta-analysis of mortality results from the four randomised controlled trials showed that those allocated to screening had a reduction in mortality from colorectal cancer of 16% (relative risk 0.84 (95% confidence interval 0.77 to 0.93)). When adjusted for attendance for screening, this reduction was 23% (relative risk 0.77 (0.57 to 0.89)) for people actually screened. If a biennial Hemoccult screening programme were offered to 10 000 people and about two thirds attended for at least one Hemoccult test, 8.5 (3.6 to 13.5) deaths from colorectal cancer would be prevented over a period of 10 years. CONCLUSION: Although benefits of screening are likely to outweigh harms for populations at high risk of colorectal cancer, more information is needed about the harmful effects of screening, the community's responses to screening, and costs of screening for different healthcare systems before widespread screening can be recommended.

Adult↗