The utility of diagnostic selective nerve root blocks in the management of patients with lumbar radiculopathy: a systematic review.

OBJECTIVE: Lumbar radiculopathy (LR) often manifests as pain in the lower back radiating into one leg (sciatica). Unsuccessful back surgery is associated with significant healthcare costs and risks to patients. This review aims to examine the diagnostic accuracy of selective nerve root blocks (SNRBs) to identify patients most likely to benefit from lumbar decompression surgery. DESIGN: Systematic review of diagnostic test accuracy studies. ELIGIBILITY CRITERIA: Primary research articles using a patient population with low back pain and symptoms in the leg, SNRB administered under radiological guidance as index test, and any reported reference standard for the diagnosis of LR. INFORMATION SOURCES: MEDLINE (Ovid), MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Science Citation Index, Biosis, LILACS, Dissertation abstracts and National Technical Information Service from inception to 2018. METHODS: Risk of bias and applicability was assessed using the QUADAS-2 tool. We performed random-effects logistic regression to meta-analyse studies grouped by reference standard. RESULTS: 6 studies (341 patients) were included in this review. All studies were judged at high risk of bias. There was substantial heterogeneity across studies in sensitivity (range 57%-100%) and specificity (10%-86%) estimates. Four studies were diagnostic cohort studies that used either intraoperative findings during surgery (pooled sensitivity: 93.5% [95% CI 84.0 to 97.6]; specificity: 50.0% [16.8 to 83.2]) or 'outcome following surgery' as the reference standard (pooled sensitivity: 90.9% [83.1 to 95.3]; specificity 22.0% [7.4 to 49.9]). Two studies had a within-patient case-control study design, but results were not pooled because different types of control injections were used. CONCLUSIONS: We found limited evidence which was of low methodological quality indicating that the diagnostic accuracy of SNRB is uncertain and that specificity in particular may be low. SNRB is a safe test with a low risk of clinically significant complications, but it remains unclear whether the additional diagnostic information it provides justifies the cost of the test.

Association Between Risk-of-Bias Assessments and Results of Randomized Trials in Cochrane Reviews: The ROBES Meta-Epidemiologic Study.

Flaws in the design of randomized trials may bias intervention effect estimates and increase between-trial heterogeneity. Empirical evidence suggests that these problems are greatest for subjectively assessed outcomes. For the Risk of Bias in Evidence Synthesis (ROBES) Study, we extracted risk-of-bias judgements (for sequence generation, allocation concealment, blinding, and incomplete data) from a large collection of meta-analyses published in the Cochrane Library (issue 4; April 2011). We categorized outcome measures as mortality, other objective outcome, or subjective outcome, and we estimated associations of bias judgements with intervention effect estimates using Bayesian hierarchical models. Among 2,443 randomized trials in 228 meta-analyses, intervention effect estimates were, on average, exaggerated in trials with high or unclear (versus low) risk-of-bias judgements for sequence generation (ratio of odds ratios (ROR) = 0.91, 95% credible interval (CrI): 0.86, 0.98), allocation concealment (ROR = 0.92, 95% CrI: 0.86, 0.98), and blinding (ROR = 0.87, 95% CrI: 0.80, 0.93). In contrast to previous work, we did not observe consistently different bias for subjective outcomes compared with mortality. However, we found an increase in between-trial heterogeneity associated with lack of blinding in meta-analyses with subjective outcomes. Inconsistency in criteria for risk-of-bias judgements applied by individual reviewers is a likely limitation of routinely collected bias assessments. Inadequate randomization and lack of blinding may lead to exaggeration of intervention effect estimates in randomized trials.

Symptomatic and quality-of-life outcomes after treatment for clinically localised prostate cancer: a systematic review.

To conduct a systematic review of the risks of short-term outcomes after major treatments for clinically localised prostate cancer. MEDLINE, EMBASE and the Cochrane Library were searched from 2004 to January 2013. Study arms that included ≥100 men with localised prostate cancer in receipt of surgery, radiotherapy or active surveillance and reported symptomatic and quality-of-life (QoL) data from 6 to 60 months after treatment were eligible. Data were extracted by one reviewer and checked by another. In all, 64 studies (80 treatment cohorts) were included. Most were single treatment cohorts from the USA or Europe. Radiotherapy was the most common treatment (40 cohorts, including 31 brachytherapy cohorts) followed by prostatectomy (39 cohorts), with only one active surveillance cohort. Most frequently measured symptoms were urinary, followed by sexual, and bowel; QoL was assessed in only 17 cohorts. Most studies used validated measures, although poor data reporting and differences between studies meant that it was not possible to pool data. Data on the precise impact of short-term symptomatic and QoL outcomes after treatment for localised prostate cancer are of insufficient quality for clear guidance to men about the risks to these aspects of their lives. It is important that future studies focus on collecting core outcomes through validated measures and comply with reporting guidelines, so that clear and accurate information can be derived for men considering screening or treatment for prostate cancer.

Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials.

BACKGROUND: Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood. METHODS: We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression. RESULTS: We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03-.25). CONCLUSIONS: Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.

Search strategies to identify diagnostic accuracy studies in MEDLINE and EMBASE.

BACKGROUND: A systematic and extensive search for as many eligible studies as possible is essential in any systematic review. When searching for diagnostic test accuracy (DTA) studies in bibliographic databases, it is recommended that terms for disease (target condition) are combined with terms for the diagnostic test (index test). Researchers have developed methodological filters to try to increase the precision of these searches. These consist of text words and database indexing terms and would be added to the target condition and index test searches.Efficiently identifying reports of DTA studies presents challenges because the methods are often not well reported in their titles and abstracts, suitable indexing terms may not be available and relevant indexing terms do not seem to be consistently assigned. A consequence of using search filters to identify records for diagnostic reviews is that relevant studies might be missed, while the number of irrelevant studies that need to be assessed may not be reduced. The current guidance for Cochrane DTA reviews recommends against the addition of a methodological search filter to target condition and index test search, as the only search approach. OBJECTIVES: To systematically review empirical studies that report the development or evaluation, or both, of methodological search filters designed to retrieve DTA studies in MEDLINE and EMBASE. SEARCH METHODS: We searched MEDLINE (1950 to week 1 November 2012); EMBASE (1980 to 2012 Week 48); the Cochrane Methodology Register (Issue 3, 2012); ISI Web of Science (11 January 2013); PsycINFO (13 March 2013); Library and Information Science Abstracts (LISA) (31 May 2010); and Library, Information Science & Technology Abstracts (LISTA) (13 March 2013). We undertook citation searches on Web of Science, checked the reference lists of relevant studies, and searched the Search Filters Resource website of the InterTASC Information Specialists' Sub-Group (ISSG). SELECTION CRITERIA: Studies reporting the development or evaluation, or both, of a MEDLINE or EMBASE search filter aimed at retrieving DTA studies, which reported a measure of the filter's performance were eligible. DATA COLLECTION AND ANALYSIS: The main outcome was a measure of filter performance, such as sensitivity or precision. We extracted data on the identification of the reference set (including the gold standard and, if used, the non-gold standard records), how the reference set was used and any limitations, the identification and combination of the search terms in the filters, internal and external validity testing, the number of filters evaluated, the date the study was conducted, the date the searches were completed, and the databases and search interfaces used. Where 2 x 2 data were available on filter performance, we used these to calculate sensitivity, specificity, precision and Number Needed to Read (NNR), and 95% confidence intervals (CIs). We compared the performance of a filter as reported by the original development study and any subsequent studies that evaluated the same filter. MAIN RESULTS: Ninteen studies were included, reporting on 57 MEDLINE filters and 13 EMBASE filters. Thirty MEDLINE and four EMBASE filters were tested in an evaluation study where the performance of one or more filters was tested against one or more gold standards. The reported outcome measures varied. Some studies reported specificity as well as sensitivity if a reference set containing non-gold standard records in addition to gold standard records was used. In some cases, the original development study did not report any performance data on the filters. Original performance from the development study was not available for 17 filters that were subsequently tested in evaluation studies. All 19 studies reported the sensitivity of the filters that they developed or evaluated, nine studies reported the specificities and 14 studies reported the precision.No filter which had original performance data from its development study, and was subsequently tested in an evaluation study, had what we defined a priori as acceptable sensitivity (> 90%) and precision (> 10%). In studies that developed MEDLINE filters that were evaluated in another study (n = 13), the sensitivity ranged from 55% to 100% (median 86%) and specificity from 73% to 98% (median 95%). Estimates of performance were lower in eight studies that evaluated the same 13 MEDLINE filters, with sensitivities ranging from 14% to 100% (median 73%) and specificities ranging from 15% to 96% (median 81%). Precision ranged from 1.1% to 40% (median 9.5%) in studies that developed MEDLINE filters and from 0.2% to 16.7% (median 4%) in studies that evaluated these filters. A similar range of specificities and precision were reported amongst the evaluation studies for MEDLINE filters without an original performance measure. Sensitivities ranged from 31% to 100% (median 71%), specificity ranged from 13% to 90% (median 55.5%) and precision from 1.0% to 11.0% (median 3.35%).For the EMBASE filters, the original sensitivities reported in two development studies ranged from 74% to 100% (median 90%) for three filters, and precision ranged from 1.2% to 17.6% (median 3.7%). Evaluation studies of these filters had sensitivities from 72% to 97% (median 86%) and precision from 1.2% to 9% (median 3.7%). The performance of EMBASE search filters in development and evaluation studies were more alike than the performance of MEDLINE filters in development and evaluation studies. None of the EMBASE filters in either type of study had a sensitivity above 90% and precision above 10%. AUTHORS' CONCLUSIONS: None of the current methodological filters designed to identify reports of primary DTA studies in MEDLINE or EMBASE combine sufficiently high sensitivity, required for systematic reviews, with a reasonable degree of precision. This finding supports the current recommendation in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy that the combination of methodological filter search terms with terms for the index test and target condition should not be used as the only approach when conducting formal searches to inform systematic reviews of DTA.

Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials.

Published evidence suggests that aspects of trial design lead to biased intervention effect estimates, but findings from different studies are inconsistent. This study combined data from 7 meta-epidemiologic studies and removed overlaps to derive a final data set of 234 unique meta-analyses containing 1973 trials. Outcome measures were classified as "mortality," "other objective," "or subjective," and Bayesian hierarchical models were used to estimate associations of trial characteristics with average bias and between-trial heterogeneity. Intervention effect estimates seemed to be exaggerated in trials with inadequate or unclear (vs. adequate) random-sequence generation (ratio of odds ratios, 0.89 [95% credible interval {CrI}, 0.82 to 0.96]) and with inadequate or unclear (vs. adequate) allocation concealment (ratio of odds ratios, 0.93 [CrI, 0.87 to 0.99]). Lack of or unclear double-blinding (vs. double-blinding) was associated with an average of 13% exaggeration of intervention effects (ratio of odds ratios, 0.87 [CrI, 0.79 to 0.96]), and between-trial heterogeneity was increased for such studies (SD increase in heterogeneity, 0.14 [CrI, 0.02 to 0.30]). For each characteristic, average bias and increases in between-trial heterogeneity were driven primarily by trials with subjective outcomes, with little evidence of bias in trials with objective and mortality outcomes. This study is limited by incomplete trial reporting, and findings may be confounded by other study design characteristics. Bias associated with study design characteristics may lead to exaggeration of intervention effect estimates and increases in between-trial heterogeneity in trials reporting subjectively assessed outcomes.

Is MRI better than CT for detecting a vascular component to dementia? A systematic review and meta-analysis.

BACKGROUND: Identification of causes of dementia soon after symptom onset is important, because appropriate treatment of some causes of dementia can slow or halt its progression or enable symptomatic treatment where appropriate. The accuracy of MRI and CT, and whether MRI is superior to CT, in detecting a vascular component to dementia in autopsy confirmed and clinical cohorts of patients with VaD, combined AD and VaD ("mixed dementia"), and AD remain unclear. We conducted a systematic review and meta-analysis to investigate this question. METHODS: We searched eight databases and screened reference lists to identify studies addressing the review question. We assessed study quality using QUADAS. We estimated summary diagnostic accuracy according to imaging finding, and ratios of diagnostic odds ratios (RDORs) for MRI versus CT and high versus low risk of bias. RESULTS: We included 7 autopsy and 31 non-autopsy studies. There was little evidence that selective patient enrolment and risk of incorporation bias impacted on diagnostic accuracy (p = 0.12 to 0.95). The most widely reported imaging finding was white matter hyperintensities. For CT (11 studies) summary sensitivity and specificity were 71% (95% CI 53%-85%) and 55% (44%-66%). Corresponding figures for MRI (6 studies) were 95% (87%-98%) and 26% (12%-50%). General infarcts was the most specific imaging finding on MRI (96%; 95% CI 94%-97%) and CT (96%; 93%-98%). However, sensitivity was low for both MRI (53%; 36%-70%) and CT (52%; 22% to 80%). No imaging finding had consistently high sensitivity. Based on non-autopsy studies, MRI was more accurate than CT for six of seven imaging findings, but confidence intervals were wide. CONCLUSION: There is insufficient evidence to suggest that MRI is superior to CT with respect to identifying cerebrovascular changes in autopsy-confirmed and clinical cohorts of VaD, AD, and 'mixed dementia'.

Selenium and prostate cancer: systematic review and meta-analysis.

BACKGROUND: Prostate cancer is a growing public health problem. Several human studies have shown a potentially protective effect of selenium, but the conclusions from published reports are inconsistent. OBJECTIVE: The objective was to examine the evidence for relations between selenium intake, selenium status, and prostate cancer risk. DESIGN: This was a systematic review and meta-analysis of randomized controlled trials, case-control studies, and prospective cohort studies. The World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project database was searched up to September 2010. The studies included reported measurements of selenium intake or status (plasma, serum, or toenail selenium), assessments of prostate cancer cases (number of events), and the RR in the adult population. Meta-analyses were performed, and study quality, heterogeneity, and small study effects were assessed. Dose-response meta-analyses were used, with restricted cubic splines and fractional polynomials for nonlinear trends, to investigate the association between selenium status and prostate cancer risk. RESULTS: Twelve studies with a total of 13,254 participants and 5007 cases of prostate cancer were included. The relation between plasma/serum selenium and prostate cancer in a nonlinear dose-response meta-analysis showed that the risk decreased with increasing plasma/serum selenium up to 170 ng/mL. Three high-quality studies included in the meta-analysis of toenail selenium and cancer risk indicated a reduction in prostate cancer risk (estimated RR: 0.29; 95% CI: 0.14, 0.61) with a toenail selenium concentration between 0.85 and 0.94 µg/g. CONCLUSION: The relation between selenium status and decreased prostate cancer risk was examined over a relatively narrow range of selenium status; further studies in low-selenium populations are required.

Associations of circulating and dietary vitamin D with prostate cancer risk: a systematic review and dose-response meta-analysis.

OBJECTIVE: We systematically reviewed and meta-analyzed literature examining associations of vitamin D (dietary intake, circulating 25-hydroxy-vitamin-D (25(OH)D), and 1,25-dihydroxy-vitamin-D (1,25(OH)(2)D) concentrations) with prostate cancer. METHODS: We searched over 24,000 papers from seven electronic databases (to October 2010) for exposures related to vitamin D. We conducted dose-response random-effects meta-analyses pooling the log odds ratio (OR) and 95% confidence intervals (CI) per change in natural units of each exposure. The I(2) statistic quantified between-study variation due to heterogeneity. RESULTS: Twenty-five papers were included. In prospective studies, the OR per 1,000 IU increase in dietary intake was 1.14 (6 studies; CI: 0.99, 1.31; I (2) = 0%) for total prostate cancer and 0.93 (3 studies; 0.63, 1.39; I (2) = 25%) for aggressive prostate cancer. Five case-control studies examined dietary intake, but there was a high degree of inconsistency between studies (I (2) = 49%). The OR per 10 ng/mL increase in 25(OH)D was 1.04 (14 studies; 0.99, 1.10; I (2) = 0%) for total prostate cancer and 0.98 (6 studies; 0.84, 1.15; I (2) = 32%) for aggressive prostate cancer. The OR per 10 pg/mL increase in 1,25(OH)(2)D was 1.00 (7 studies; 0.87, 1.14; I (2) = 41%) for total prostate cancer and 0.86 (2 studies; 0.72, 1.02; I (2) = 0%) for aggressive prostate cancer. CONCLUSION: Published literature provides little evidence to support a major role of vitamin D in preventing prostate cancer or its progression.

Inclusion of methodological filters in searches for diagnostic test accuracy studies misses relevant studies.

OBJECTIVE: To compare the performance of MEDLINE searches using index test(s) and target condition (subject searches) with the same searches combined with methodological filters for test accuracy studies. STUDY DESIGN AND SETTING: We derived a reference set of 506 test accuracy studies indexed on MEDLINE from seven systematic reviews that conducted extensive searches. We compared the performance of "subject" with "filtered" searches (same searches combined with each of 22 filters). Outcome measures were number of reference set records missed, sensitivity, number needed to read (NNR), and precision (Number of reference set studies identified for every 100 records screened). RESULTS: Subject searches missed 47 of the 506 reference studies; filtered searches missed an additional 21 to 241 studies. Sensitivity was 91% for subject searches and ranged from 43% to 87% for filtered searches. The NNR was 56 (precision 2%) for subject searches and ranged from 7 to 51 (precision 2-15%) for filtered searches. CONCLUSIONS: Filtered searches miss additional studies compared with searches based on index test and target condition. None of the existing filters provided reductions in the NNR for acceptable sensitivity; currently available methodological filters should not be used to identify studies for inclusion in test accuracy reviews.

Systematic review: accuracy of anti-citrullinated Peptide antibodies for diagnosing rheumatoid arthritis.

BACKGROUND: Early recognition and treatment of rheumatoid arthritis is important to prevent irreversible joint damage. Anti-citrullinated peptide antibodies (ACPA) have been suggested for early diagnosis. PURPOSE: To compare the accuracy of ACPA and rheumatoid factor in diagnosing rheumatoid arthritis in patients with early symptoms of the disease. DATA SOURCES: 10 medical databases from inception to September 2009, with no language or publication restrictions, and references of included studies. STUDY SELECTION: Two independent reviewers screened searches. Full articles were assessed by one reviewer and checked by a second reviewer to identify studies that reported 2 x 2 data on ACPA for the diagnosis of rheumatoid arthritis (by 1987 American College of Rheumatology criteria). DATA EXTRACTION: One reviewer abstracted data on patient characteristics, ACPA details, and 2 x 2 data and assessed study quality by using the QUADAS tool. A second reviewer checked extractions. DATA SYNTHESIS: 151 studies were included, with considerable heterogeneity in sensitivity (range, 12% to 93%) and specificity (range, 63% to 100%). In cohort studies that investigated second-generation anti-cyclic citrullinated peptide antibodies (anti-CCP2) in patients with early rheumatoid arthritis (<2 years), summary sensitivity and specificity were 57% (95% CI, 51% to 63%) and 96% (CI, 93% to 97%), respectively. Case-control and cross-sectional studies and studies of patients with established rheumatoid arthritis all overestimated sensitivity. Anti-CCP2 had greater specificity than rheumatoid factor (96% vs. 86%), with similar sensitivity. Evidence was insufficient to ascertain whether the combination of anti-CCP2 and rheumatoid factor provides additional benefit over anti-CCP2 alone. LIMITATIONS: Most studies used a diagnostic case-control design, which overestimated sensitivity. Items relating to study quality were rarely reported. Publication bias could not be assessed. CONCLUSION: Anti-CCP2 should be included in the work-up of patients with early symptoms of rheumatoid arthritis.

Development of a combined database for meta-epidemiological research.

Collections of meta-analyses assembled in meta-epidemiological studies are used to study associations of trial characteristics with intervention effect estimates. However, methods and findings are not consistent across studies. To combine data from 10 meta-epidemiological studies into a single database, and derive a harmonized dataset without overlap between meta-analyses. The database design allowed trials to be contained in different meta-analyses, multiple meta-analyses in systematic reviews, overlapping meta-analyses between systematic reviews, and multiple references to the same trial or review. Unique identifiers were assigned to each reference and used to identify duplicate trials. Sets of meta-analyses with overlapping trials were identified and duplicates removed. Overlapping trials were used to examine agreement between assessments of trial characteristics. The combined database contained 427 reviews, 454 meta-analyses and 4874 trial results. Of these, 258 meta-analyses were unique, while for 196 at least one trial overlapped with another meta-analysis. Median kappa statistics for reliability of assessments were 0.60 for sequence generation, 0.58 for allocation concealment and 0.87 for blinding. Based on inspection of sets of overlapping meta-analyses, 91 meta-analyses containing 1344 trial results were removed. Additionally, 24 duplicated trial results were removed from 16 meta-analyses, to derive a final database containing 363 meta-analyses and 3477 unique trial results. The final database will be used to examine the combined evidence on sources of bias in randomized controlled trials. The strategy used to remove overlap between meta-analyses may be of use for future empirical research. Copyright © 2010 John Wiley & Sons, Ltd.

Height and prostate cancer risk: a large nested case-control study (ProtecT) and meta-analysis.

BACKGROUND: Height, a marker of childhood environmental exposures, is positively associated with prostate cancer risk, perhaps through the insulin-like growth factor system. We investigated the relationship of prostate cancer with height and its components (leg and trunk length) in a nested case-control study and with height in a dose-response meta-analysis. METHODS: We nested a case-control study within a population-based randomized controlled trial evaluating treatments for localized prostate cancer in British men ages 50 to 69 years, including 1,357 cases detected through prostate-specific antigen testing and 7,990 controls (matched on age, general practice, assessment date). Nine bibliographic databases were searched systematically for studies on the height-prostate cancer association that were pooled in a meta-analysis. RESULTS: Based on the nested case-control, the odds ratio (OR) of prostate-specific antigen-detected prostate cancer per 10 cm increase in height was 1.06 [95% confidence interval (95% CI): 0.97-1.16; p(trend) = 0.2]. There was stronger evidence of an association of height with high-grade prostate cancer (OR: 1.23; 95% CI: 1.06-1.43), mainly due to the leg component, but not with low-grade disease (OR: 0.99; 95% CI: 0.90-1.10). In general, associations with leg or trunk length were similar. A meta-analysis of 58 studies found evidence that height is positively associated with prostate cancer (random-effects OR per 10 cm: 1.06; 95% CI: 1.03-1.09), with a stronger effect for prospective studies of more advanced/aggressive cancers (random-effects OR: 1.12; 95% CI: 1.05-1.19). CONCLUSION: These data indicate a limited role for childhood environmental exposures-as indexed by adult height-on prostate cancer incidence, while suggesting a greater role for progression, through mechanisms requiring further investigation.

How much of the data published in observational studies of the association between diet and prostate or bladder cancer is usable for meta-analysis?

Epidemiologic investigations often report dose-response associations, which may be combined in meta-analyses. The authors examined how often the log odds, risk, or hazard ratio per unit increase in exposure, and its standard error, can be estimated from results reported from observational studies of diet and prostate or bladder cancer so that results are usable in meta-analyses estimating dose-response associations. Eight electronic databases were searched for studies reporting on the association of diet, nutrition, or physical activity with these cancers. A total of 767 papers reported 3,284 results; 1,999 (61%) results, reported in 545 (71%) papers, were usable in dose-response meta-analyses. The most important reason that results were not usable was the absence of sufficient information on exposure levels in the different groups. The proportion of results usable in "high-low" meta-analyses (comparisons of extreme categories) was similar (62%). Results that showed evidence of an association were more likely to be usable than results that found no such evidence. Insufficient detail in reporting of results of observational studies can lead to exclusion of these results from meta-analyses and is an important threat to the validity of systematic reviews of such research. Results providing evidence of associations may be overrepresented in meta-analyses of observational studies.

Nutritional interventions and outcome in patients with cancer or preinvasive lesions: systematic review.

BACKGROUND: Dietary modifications and supplements are used widely by patients with cancer and preinvasive lesions as an adjunct to standard treatment. Given the widespread use of nutritional modifications and supplements by such patients and concerns about the lack of benefit and possible harm, we conducted a systematic review of randomized controlled trials to examine the effect of nutritional interventions on patients with cancer or preinvasive lesions. METHODS: We searched electronic databases and reference lists to locate all eligible trials and analyzed trial quality. Outcome measures were all-cause and cancer mortality, disease-free survival, cancer recurrence, second primary cancer, recurrence of a preinvasive lesion, or progression to cancer. Results of individual trials were combined by use of random-effects meta-analyses. RESULTS: We identified 59 eligible trials, 25 in patients with cancer and 34 in patients with preinvasive lesions, respectively. Trial quality was generally low; only three trials (two of cancer and one of preinvasive lesions) had adequate methods for generating the allocation sequence, allocation concealment, and masking both outcome assessors and participants. The combined odds ratio (OR) for the effect of a healthy diet-given alone or with dietary supplements, weight loss, or exercise-on all-cause mortality was 0.90 (95% confidence interval [CI] = 0.46 to 1.77). There was no evidence of an association between the use of antioxidant (OR = 1.01, 95% CI = 0.88 to 1.15) or retinol (OR = 0.97, 95% CI = 0.83 to 1.13) supplements and all-cause mortality. Meta-analyses of all other outcomes did not show clear evidence of benefit or harm. CONCLUSIONS: The impact of most nutritional interventions cannot be reliably estimated because of the limited number of trials, many of which were of low quality. There is no evidence that dietary modification by cancer patients improves survival and benefits disease prognosis.