PubMed Health⌕ Search

Biomedical subjects

Jonathan J Deeks

Publications and source records attributed to Jonathan J Deeks.

At least 19 recordsLinked to original sources
PubMed2007

Much ado about nothing: a comparison of the performance of meta-analytical methods with rare events.

For rare outcomes, meta-analysis of randomized trials may be the only way to obtain reliable evidence of the effects of healthcare interventions. However, many methods of meta-analysis are based on large sample approximations, and may be unsuitable when events are rare. Through simulation, we evaluated the performance of 12 methods for pooling rare events, considering estimability, bias, coverage and statistical power. Simulations were based on data sets from three case studies with between five and 19 trials, using baseline event rates between 0.1 and 10 per cent and risk ratios of 1, 0.75, 0.5 and 0.2. We found that most of the commonly used meta-analytical methods were biased when data were sparse. The bias was greatest in inverse variance and DerSimonian and Laird odds ratio and risk difference methods, and the Mantel-Haenszel (MH) odds ratio method using a 0.5 zero-cell correction. Risk difference meta-analytical methods tended to show conservative confidence interval coverage and low statistical power at low event rates. At event rates below 1 per cent the Peto one-step odds ratio method was the least biased and most powerful method, and provided the best confidence interval coverage, provided there was no substantial imbalance between treatment and control group sizes within trials, and treatment effects were not exceptionally large. In other circumstances the MH OR without zero-cell corrections, logistic regression and the exact method performed similarly to each other, and were less biased than the Peto method.

Analysis of Variance↗
PubMed2006

Effect of needle size on immunogenicity and reactogenicity of vaccines in infants: randomised controlled trial.

OBJECTIVES: To assess the immunogenicity of vaccines for infants and to investigate whether the incidence of reactogenicity is reduced after each immunisation dose using needles of varying lengths and gauges. DESIGN: Randomised controlled trial. SETTING: 18 general practices within two UK primary care trusts. PARTICIPANTS: 696 healthy infants vaccinated at 2, 3, and 4 months of age, with follow-up to 5 months of age. INTERVENTIONS: Combined diphtheria, tetanus, whole cell pertussis, and Haemophilus influenzae type b vaccine and a serogroup C meningococcal glycoconjugate vaccine administered using either a wide, long needle (23 gauge/0.6 mm diameter, 25 mm), a narrow, short needle (25 gauge/0.5 mm diameter, 16 mm), or a narrow, long needle (25 gauge, 25 mm). MAIN OUTCOME MEASURES: Local and general reactions recorded by parents for three days after each dose; and diphtheria, tetanus, and H influenzae type b antibody concentrations and functional antibody against serogroup C Neisseria meningitidis 28-42 days after the third dose. RESULTS: Local reactions to diphtheria, tetanus, whole cell pertussis, H influenzae type b vaccinations decreased significantly with wide, long needles compared with narrow, short needles. At all three doses one less infant experienced local reactions at days 1, 2, or 3 for every six to eight vaccinated. Significantly fewer infants vaccinated with the long needle experienced severe local reactions. Non-inferiority of the immune response was shown using a wide, long needle rather than a narrow, short needle for serogroup C meningococcal glycoconjugate vaccine and for diphtheria but not for H influenzae type b or tetanus, although no evidence was found of a decrease. Little difference was found between needles of the same length but different gauges in local reaction or immune response. CONCLUSIONS: Long (25 mm) needles for infant immunisations can significantly reduce vaccine reactogenicity at each dose while achieving comparable immunogenicity to that of short (16 mm) needles. Trial registration Current Controlled Trials ISRCTN62032215 [controlled-trials.com].

Diphtheria-Tetanus-Pertussis Vaccine↗
PubMed2006

Systematic reviews of diagnostic tests in cancer: review of methods and reporting.

OBJECTIVES: To assess the methods and reporting of systematic reviews of diagnostic tests. DATA SOURCES: Systematic searches of Medline, Embase, and five other databases identified reviews of tests used in patients with cancer. Of these, 89 satisfied our inclusion criteria of reporting accuracy of the test compared with a reference test, including an electronic search, and published since 1990. REVIEW METHODS: All reviews were assessed for methods and reporting of objectives, search strategy, participants, clinical setting, index and reference tests, study design, study results, graphs, meta-analysis, quality, bias, and procedures in the review. We assessed 25 randomly selected reviews in more detail. RESULTS: 75% (67) of the reviews stated inclusion criteria, 49% (44) tabulated characteristics of included studies, 40% (36) reported details of study design, 17% (15) reported on the clinical setting, 17% (15) reported on the severity of disease in participants, and 49% (44) reported on whether the tumours were primary, metastatic, or recurrent. Of the 25 reviews assessed in detail, 68% (17) stated the reference standard used in the review, 36% (9) reported the definition of a positive result for the index test, and 56% (14) reported sensitivity, specificity, and sample sizes for individual studies. Of the 89 reviews, 61% (54) attempted to formally synthesise results of the studies and 32% (29) reported formal assessments of study quality. CONCLUSIONS: Reliability and relevance of current systematic reviews of diagnostic tests is compromised by poor reporting and review methods.

Bias↗
PubMed2006

Dynamic antigen-specific T-cell responses after point-source exposure to Mycobacterium tuberculosis.

RATIONALE: The kinetics of Mycobacterium tuberculosis-specific Th1-type T-cell responses after M. tuberculosis infection are likely to be important in determining clinical outcome. OBJECTIVE: To investigate the kinetics of T-cell responses, in the context of a point-source school tuberculosis outbreak, in three groups of contacts who differed by preventive treatment status and tuberculin skin test (TST) results: 38 treated TST-positive students, 11 untreated TST-positive staff, and 14 untreated students with negative or borderline TST results. METHODS: We used the ex vivo IFN-gamma enzyme-linked immunospot assay (ELISpot) to track T cells specific for two region of difference 1 (RD1) antigens, early secretory antigenic target 6 and culture filtrate protein 10, for 18 mo after cessation of tuberculosis exposure. MAIN RESULTS: The treated TST-positive students had an average 68% decline in frequencies of RD1-specific IFN-gamma-secreting T cells per year (p < 0.0001) and 6 of 38 students had no detectable RD1-specific T cells by 18 mo. No change in frequencies of these cells was observed in the untreated TST-positive staff (p = 0.38) and none were ELISpot-negative at 18 mo. Of the 14 untreated students, 7 were persistently ELISpot-positive (all of whom had borderline TST results), and 7 became ELISpot-negative (all but one had negative TST results) during follow-up. CONCLUSIONS: The decrease in M. tuberculosis-specific T cells and their disappearance in a proportion of treated students likely reflect declining antigenic and bacterial load in vivo induced by antibiotic treatment. The observed disappearance of M. tuberculosis-specific T cells in the untreated TST-negative contacts suggests that an acute resolving infection may occur in some contacts.

Adult↗
PubMed2006

A unification of models for meta-analysis of diagnostic accuracy studies.

Studies of diagnostic accuracy require more sophisticated methods for their meta-analysis than studies of therapeutic interventions. A number of different, and apparently divergent, methods for meta-analysis of diagnostic studies have been proposed, including two alternative approaches that are statistically rigorous and allow for between-study variability: the hierarchical summary receiver operating characteristic (ROC) model (Rutter and Gatsonis, 2001) and bivariate random-effects meta-analysis (van Houwelingen and others, 1993), (van Houwelingen and others, 2002), (Reitsma and others, 2005). We show that these two models are very closely related, and define the circumstances in which they are identical. We discuss the different forms of summary model output suggested by the two approaches, including summary ROC curves, summary points, confidence regions, and prediction regions.

Diagnostic Tests, Routine↗
PubMed2006

Accuracy of magnetic resonance imaging for the diagnosis of multiple sclerosis: systematic review.

OBJECTIVE: To determine the accuracy of magnetic resonance imaging criteria for the early diagnosis of multiple sclerosis in patients with suspected disease. DESIGN: Systematic review. DATA SOURCES: 12 electronic databases, citation searches, and reference lists of included studies. Review methods Studies on accuracy of diagnosis that compared magnetic resonance imaging, or diagnostic criteria incorporating such imaging, to a reference standard for the diagnosis of multiple sclerosis. RESULTS: 29 studies (18 cohort studies, 11 other designs) were included. On average, studies of other designs (mainly diagnostic case-control studies) produced higher estimated diagnostic odds ratios than did cohort studies. Among 15 studies of higher methodological quality (cohort design, clinical follow-up as reference standard), those with longer follow-up produced higher estimates of specificity and lower estimates of sensitivity. Only two such studies followed patients for more than 10 years. Even in the presence of many lesions (> 10 or > 8), magnetic resonance imaging could not accurately rule multiple sclerosis in (likelihood ratio of a positive test result 3.0 and 2.0, respectively). Similarly, the absence of lesions was of limited utility in ruling out a diagnosis of multiple sclerosis (likelihood ratio of a negative test result 0.1 and 0.5). CONCLUSIONS: Many evaluations of the accuracy of magnetic resonance imaging for the early detection of multiple sclerosis have produced inflated estimates of test performance owing to methodological weaknesses. Use of magnetic resonance imaging to confirm multiple sclerosis on the basis of a single attack of neurological dysfunction may lead to over-diagnosis and over-treatment.

Case-Control Studies↗
PubMed2006

A critical appraisal of the Australian comparative trial of methadone and buprenorphine maintenance.

While there are serious problems with the analyses and reports, the Australian comparative trial of methadone and buprenorphine maintenance has generated very useful data. Contrary to the triallists' conclusions, their study provides good evidence that methadone is better than buprenorphine at retaining addicts in programmes where clinicians can adjust their patients' daily doses. The trial also provides the first evidence that methadone is significantly cheaper than buprenorphine maintenance. The savings from less frequent clinic attendance were more than offset by the extra time spent dispensing buprenorphine and the greater cost of the buprenorphine itself. In cost-effectiveness terms, the trial's results show methadone 'dominates' buprenorphine as an opioid maintenance drug because it is not only more effective but also cheaper.

Australia↗
PubMed2006

An assessment of the publicly disseminated evidence of safety used in decisions to withdraw medicinal products from the UK and US markets.

BACKGROUND: The objective of this study was to assess the publicly disseminated evidence used to support decisions to withdraw medicinal products for safety reasons, and related implications for the conduct of systematic reviews of harm. METHODS: Medicinal products withdrawn from the UK and US markets for safety reasons were identified from websites of the UK Medicines Control Agency (now known as the Medicines and Healthcare products Regulatory Agency) and the US FDA. Related scientific evidence was identified from communications made to the public and healthcare professionals at the time of each product withdrawal. Evidence for each product withdrawal decision was classified according to study design and outcome. RESULTS: Eleven products were withdrawn during 1999-2001. Randomised trial evidence was cited for two products (18%) and comparative observational studies for two products (18%). Evidence from spontaneous reports supported the withdrawal of eight products (73%), with four products (36%) apparently withdrawn on the basis of spontaneous reports alone. Only two products (18%) were withdrawn on evidence for a patient relevant outcome from comparative studies. CONCLUSIONS: It is rare that evidence other than spontaneous reports is cited in support of drug withdrawals. The serious implications of product withdrawal mandate the elevation of the level of evidence that supports such public health decisions. Once suspicions of important safety hazards have emerged, prospective studies may be unfeasible and may be seen as unethical. Prospective studies can strengthen the evidence base and should be planned to commence when every drug is first marketed. Systematic reviews are unlikely to elicit evidence of harm associated with a drug unless they include spontaneous reports and surrogate outcomes.

Consumer Product Safety↗
PubMed2005

The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed.

BACKGROUND AND OBJECTIVE: Publication bias and other sample size effects are issues for meta-analyses of test accuracy, as for randomized trials. We investigate limitations of standard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods. METHODS: Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy. RESULTS: Type I error rates for the Begg, Egger, and Macaskill tests are inflated for typical diagnostic odds ratios (DOR), when disease prevalence differs from 50% and when thresholds favor sensitivity over specificity or vice versa. Regression and correlation tests based on functions of effective sample size are valid, if occasionally conservative, tests for sample size effects. Empirical evidence suggests that they have adequate power to be useful tests. When DORs are heterogeneous, however, all tests of funnel plot asymmetry have low power. CONCLUSION: Existing tests that use standard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy. The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects.

Diagnostic Errors↗
PubMed2005

Acquisition of Streptococcus pneumoniae and nonspecific morbidity in infants and their families: a cohort study.

BACKGROUND: Most children are believed to acquire Streptococcus pneumoniae asymptomatically, with only a few developing overt S. pneumoniae disease. This study investigates the relationship between acquisition of S. pneumoniae and mild nonspecific infection leading to general practitioner (GP) consultation. METHODS: A prospective birth cohort study of 213 infants assessed at home 9 times during 24 weeks by nasopharyngeal swab and parental interview was conducted. RESULTS: All positive S. pneumoniae swabs (including acquisition and carriage) were significantly associated with GP consultations for infection by the study infant compared with infants with negative swabs [odds ratio (OR), 1.6; 95% confidence interval (CI) 1.1-2.2; P = 0.005]. There was a stronger association with S. pneumoniae acquisition alone (OR 2.1; 95% CI 1.3-3.4; P = 0.001) than with carriage only (OR 1.4; 95% CI 0.9-2.0; P = 0.1). Multivariate analysis confirmed that S. pneumoniae acquisition by the study subject was independently associated with GP consultations: adjusted hazard ratio, 1.8 (95% CI 1.1-2.9); P = 0.02. A similar and independent association was found between S. pneumoniae acquisition by the study subject, and GP consultations for infection by the family (adjusted hazard ratio, 1.8; 95% CI 1.1-2.8; P = 0.01). CONCLUSION: Acquisition of S. pneumoniae by the study infant was significantly associated with GP consultations for infection by the infant or family.

Carrier State↗
PubMed2005

CT colonography in the detection of colorectal polyps and cancer: systematic review, meta-analysis, and proposed minimum data set for study level reporting.

PURPOSE: To assess the methodologic quality of available data in published reports of computed tomographic (CT) colonography by performing systematic review and meta-analysis. MATERIALS AND METHODS: The MEDLINE database was searched for colonography reports published between 1994 and 2003, without language restriction. The terms colonography, colography, CT colonoscopy, CT pneumocolon, virtual colonoscopy, and virtual endoscopy were used. Studies were selected if the focus was detection of colorectal polyps verified with within-subject reference colonoscopy by using key methodologic criteria based on information presented at the Fourth International Symposium on Virtual Colonoscopy (Boston, Mass). Two reviewers independently abstracted methodologic characteristics. Per-patient and per-polyp detection rates were extracted, and authors were contacted, when necessary. Per-patient sensitivity and specificity were calculated for different lesion size categories, and Forest plots were produced. Meta-analysis of paired sensitivity and specificity was conducted by using a hierarchical model that enabled estimation of summary receiver operating characteristic curves allowing for variation in diagnostic threshold, and the average operating point was calculated. Per-polyp sensitivity was also calculated. RESULTS: Of 1398 studies considered for inclusion, 24 met our criteria. There were 4181 patients with a study prevalence of abnormality of 15%-72%. Meta-analysis of 2610 patients, 206 of whom had large polyps, showed high per-patient average sensitivity (93%; 95% confidence interval [CI]: 73%, 98%) and specificity (97%; 95% CI: 95%, 99%) for colonography; sensitivity and specificity decreased to 86% (95% CI: 75%, 93%) and 86% (95% CI: 76%, 93%), respectively, when the threshold was lowered to include medium polyps. When polyps of all sizes were included, studies were too heterogeneous in sensitivity (range, 45%-97%) and specificity (range, 26%-97%) to allow meaningful meta-analysis. Of 150 cancers, 144 were detected (sensitivity, 95.9%; 95% CI: 91.4%, 98.5%). Data reporting was frequently incomplete, with no generally accepted format. CONCLUSION: CT colonography seems sufficiently sensitive and specific in the detection of large and medium polyps; it is especially sensitive in the detection of symptomatic cancer. Studies are poorly reported, however, and the authors propose a minimum data set for study reporting.

Colonic Polyps↗
PubMed2005

Schizophrenia and suicide: systematic review of risk factors.

BACKGROUND: Suicide risk is greatly increased in schizophrenia. Detection of those at risk is clinically important. AIMS: To identify risk factors for suicide in schizophrenia. METHOD: The international literature on case-control and cohort studies of patients with schizophrenia or related conditions in which suicide was reported as an outcome was systematically reviewed. Studies were identified through searching electronic databases and reference lists, and by consulting experts. RESULTS: Twenty-nine eligible studies were identified. Factors with robust evidence of increased risk of suicide were previous depressive disorders (OR=3.03, 95% CI 2.06-4.46), previous suicide attempts (OR=4.09, 95% CI 2.79-6.01), drug misuse (OR=3.21, 95% CI 1.99-5.17), agitation or motor restlessness (OR=2.61, 95% CI 1.54-4.41), fear of mental disintegration (OR=12.1, 95% CI 1.89-81.3), poor adherence to treatment (OR=3.75, 95% CI 2.20-6.37) and recent loss (OR=4.03, 95% CI 1.37-11.8). Reduced risk was associated with hallucinations (OR=0.50, 95% CI 0.35-0.71). CONCLUSIONS: Prevention of suicide in schizophrenia is likely to result from treatment of affective symptoms, improving adherence to treatment, and maintaining special vigilance in patients with risk factors, especially after losses.

Depressive Disorder↗
PubMed2004

Effects of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review.

OBJECTIVE: To evaluate the effects of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (AIIRAs) on renal outcomes and all cause mortality in patients with diabetic nephropathy. DATA SOURCES: Medline, Embase, the Cochrane controlled trials register, conference proceedings, and contact with investigators. STUDY SELECTION: Trials comparing ACE inhibitors or AIIRAs with placebo or with each other in patients with diabetic nephropathy. DATA EXTRACTION: Mortality, renal outcomes (end stage renal disease, doubling of serum creatinine concentration, prevention of progression of microalbuminuria to macroalbuminuria, remission of microalbuminuria), and quality of trials. DATA SYNTHESIS: 36 of 43 identified trials compared ACE inhibitors with placebo (4008 patients), four compared AIIRAs with placebo (3331 patients), and three compared ACE inhibitors with AIIRAs (206 patients). We obtained unpublished data for 11 trials. ACE inhibitors significantly reduced all cause mortality (relative risk 0.79, 95% confidence interval 0.63 to 0.99) compared with placebo but AIIRAs did not (0.99, 0.85 to 1.17), although baseline mortality was similar in the trials. Both agents had similar effects on renal outcomes. Reliable estimates of the unconfounded relative effects of ACE inhibitors compared with AIIRAs could not be obtained owing to small sample sizes. CONCLUSION: Although the survival benefits of ACE inhibitors for patients with diabetic nephropathy are known, the relative effects of ACE inhibitors and AIIRAs on survival are unknown owing to the lack of adequate head to head trials.

Angiotensin II Type 2 Receptor Blockers↗
PubMed2003

Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses.

OBJECTIVE: To determine the validity of adjusted indirect comparisons by using data from published meta-analyses of randomised trials. DESIGN: Direct comparison of different interventions in randomised trials and adjusted indirect comparison in which two interventions were compared through their relative effect versus a common comparator. The discrepancy between the direct and adjusted indirect comparison was measured by the difference between the two estimates. DATA SOURCES: Database of abstracts of reviews of effectiveness (1994-8), the Cochrane database of systematic reviews, Medline, and references of retrieved articles. RESULTS: 44 published meta-analyses (from 28 systematic reviews) provided sufficient data. In most cases, results of adjusted indirect comparisons were not significantly different from those of direct comparisons. A significant discrepancy (P<0.05) was observed in three of the 44 comparisons between the direct and the adjusted indirect estimates. There was a moderate agreement between the statistical conclusions from the direct and adjusted indirect comparisons (kappa 0.51). The direction of discrepancy between the two estimates was inconsistent. CONCLUSIONS: Adjusted indirect comparisons usually but not always agree with the results of head to head randomised trials. When there is no or insufficient direct evidence from randomised trials, the adjusted indirect comparison may provide useful or supplementary information on the relative efficacy of competing interventions. The validity of the adjusted indirect comparisons depends on the internal validity and similarity of the included trials.

Data Interpretation, Statistical↗