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Biomedical subjects

J Kleijnen

Publications and source records attributed to J Kleijnen.

At least 19 recordsLinked to original sources

A systematic review of lay views about infant size and growth.

OBJECTIVES: To understand lay views on infant size and growth and their implications for a British population. METHODS: A systematic review of parental and other lay views about the meanings and importance of infant size and growth using Medline, PsycInfo, CINAHL, Sociological Abstracts, IBSS, ASSIA, British Nursing Index ChildData, Caredata, SIGLE, Dissertation Abstracts (US), Index to Theses. 19 studies, most of which reported the views of mothers, from the US, Canada, the UK and Finland were reviewed. RESULTS: Notions of healthy size and growth were dominated by the concept of normality. Participants created norms by assessing and comparing size and growth against several reference points. When size or growth differed from these norms, explanations were sought for factors that would account for this difference. When no plausible explanation could be found, growth or size became a worry for parents. CONCLUSIONS: Parents consider the importance of contextual factors when judging what is appropriate or healthy growth. For public health advice to be effective, lay, as well as scientific, findings and values need to be considered.

Anthropometry↗

A systematic review of the effectiveness and cost-effectiveness of neuroimaging assessments used to visualise the seizure focus in people with refractory epilepsy being considered for surgery.

OBJECTIVE: To review the effectiveness and/or accuracy, cost-effectiveness, and predictive value of neuroimaging of the cerebral cortex to visualise the seizure focus in people with refractory epilepsy being considered for surgery. DATA SOURCES: Electronic databases, Internet searches, hand searching and consultation with experts. METHODS: A systematic review was undertaken according to published guidelines. Results of diagnostic accuracy studies were analysed according to the imaging test evaluated. For each study the proportion of patients who were correctly localised, not localised, partially localised or incorrectly localised by the index test was calculated. Due to the heterogeneity present between studies, statistical pooling was not performed. Instead, a narrative synthesis of results is presented. For studies using multivariate analysis to look at the association of neuroimaging findings and outcome following surgery, all factors considered in the analyses were presented. Studies were grouped according to the neuroimaging technique investigated and the findings discussed with reference to possible sources of heterogeneity between studies. RESULTS: No randomised controlled trials (RCTs) were identified, with the majority of studies evaluating the diagnostic accuracy of various imaging techniques in the localisation of epileptic seizure foci. There was significant heterogeneity (p<0.05) between studies for at least one of the localisation categories (correctly localised, not localised, partially localised and incorrectly localised) for all imaging techniques. Possible explanations for this heterogeneity include differing study designs, index test characteristics, reference standards and population characteristics. Test performance was more promising in studies restricted to patients with temporal lobe epilepsy. Ictal single photon emission computed tomography (SPECT) generally had more correctly localising (70--100%) and fewer non-localising (0--7%) scans than other techniques evaluated in patients with temporal lobe epilepsy. Results for computed tomography and interictal SPECT suggest that these tests are relatively poor at localising the seizure focus. Volumeric magnetic resonance imaging (MRI) and position emission tomography (PET) appear promising, and subtraction ictal single photon emission computed tomography co-registered to magnetic resonance imaging (SISCOM) and magnetic resonance spectrosopy (MRS) less promising than ictal SPECT, but these technologies have been assessed in fewer studies. T2 relaxometry was reported in only one small study with inconclusive results. Seventeen studies (33 evaluations) provided sufficient data on the association of a localised scan with outcome following surgery to calculate a relative risk. The majority of evaluations (24/33) suggested that patients with a correctly or partially localised scan had a better outcome following surgery than those with an incorrectly localised or non-localised scan. However, this association was statistically significant in only three studies, two evaluating routine MRI [(relative risk (RR) 2.74, 95% confidence interval (CI): 1.32 to 5.67; RR 1.28, 95% CI: 1.00 to 1.63] and the other SISCOM (RR 2.12, 95% CI: 1.01, 4.44). Nine studies used multivariate analysis to investigate the association of MRI (7 studies), MRS and volumetric MRI (1 study), PET (3 studies), SPECT (1 study) and SISCOM (3 studies) with the outcome following surgery. There was a trend for localisation of abnormalities to be associated with a beneficial outcome. CONCLUSIONS: Due to the limitations of the included studies, the results of this review do little to inform clinical practice, with insufficient evidence regarding effectiveness and cost-effectiveness of imaging techniques in the work-up for epilepsy surgery. Given the inadequacy of existing data, there is a pressing need for studies investigating the utility of imaging techniques in the work up for epilepsy surgery. The most reliable method to achieve this is the RCT, which could examine the single tests or combinations of tests on patient outcome. The authors suggest that it is important that clinicians, patient groups, policy makers and healthcare/research funders meet and debate the most appropriate way to investigate these technologies.

Cerebral Cortex↗

Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation.

OBJECTIVES: To determine the most effective diagnostic strategy for the investigation of microscopic and macroscopic haematuria in adults. DATA SOURCES: Electronic databases from inception to October 2003, updated in August 2004. REVIEW METHODS: A systematic review was undertaken according to published guidelines. Decision analytic modelling was undertaken, based on the findings of the review, expert opinion and additional information from the literature, to assess the relative cost-effectiveness of plausible alternative tests that are part of diagnostic algorithms for haematuria. RESULTS: A total of 118 studies met the inclusion criteria. No studies that evaluated the effectiveness of diagnostic algorithms for haematuria or the effectiveness of screening for haematuria or investigating its underlying cause were identified. Eighteen out of 19 identified studies evaluated dipstick tests and data from these suggested that these are moderately useful in establishing the presence of, but cannot be used to rule out, haematuria. Six studies using haematuria as a test for the presence of a disease indicated that the detection of microhaematuria cannot alone be considered a useful test either to rule in or rule out the presence of a significant underlying pathology (urinary calculi or bladder cancer). Forty-eight of 80 studies addressed methods to localise the source of bleeding (renal or lower urinary tract). The methods and thresholds described in these studies varied greatly, precluding any estimate of a 'best performance' threshold that could be applied across patient groups. However, studies of red blood cell morphology that used a cut-off value of 80% dysmorphic cells for glomerular disease reported consistently high specificities (potentially useful in ruling in a renal cause for haematuria). The reported sensitivities were generally low. Twenty-eight studies included data on the accuracy of laboratory tests (tumour markers, cytology) for the diagnosis of bladder cancer. The majority of tumour marker studies evaluated nuclear matrix protein 22 or bladder tumour antigen. The sensitivity and specificity ranges suggested that neither of these would be useful either for diagnosing bladder cancer or for ruling out patients for further investigation (cystoscopy). However, the evidence remains sparse and the diagnostic accuracy estimates varied widely between studies. Fifteen studies evaluating urine cytology as a test for urinary tract malignancies were heterogeneous and poorly reported. The calculated specificity values were generally high, suggesting some possible utility in confirming malignancy. However, the evidence suggests that urine cytology has no application in ruling out malignancy or excluding patients from further investigation. Fifteen studies evaluated imaging techniques [computed tomography (CT), intravenous urography (IVU) or ultrasound scanning (US)] to detect the underlying cause of haematuria. The target condition and the reference standard varied greatly between these studies. The diagnostic accuracy data for several individual studies appeared promising but meaningful comparison of the available imaging technologies was impossible. Eight studies met the inclusion criteria but addressed different parts of the diagnostic chain (e.g. screening programmes, laboratory investigations, full urological work-up). No single study addressed the complete diagnostic process. The review also highlighted a number of methodological limitations of these studies, including their lack of generalisability to the UK context. Separate decision analytic models were therefore developed to progress estimation of the optimal strategy for the diagnostic management of haematuria. The economic model for the detection of microhaematuria found that immediate microscopy following a positive dipstick test would improve diagnostic efficiency as it eliminates the high number of false positives produced by dipstick testing. Strategies that use routine microscopy may be associated with high numbers of false results, but evidence was lacking regarding the accuracy of routine microscopy and estimates were adopted for the model. The model for imaging the upper urinary tract showed that US detects more tumours than IVU at one-third of the cost, and is also associated with fewer false results. For any cause of haematuria, CT was shown to have a mean incremental cost-effectiveness ratio of pounds sterling 9939 in comparison with the next best option, US. When US is followed up with CT for negative results with persistent haematuria, it dominates the initial use of CT alone, with a saving of pounds sterling 235,000 for the evaluation of 1000 patients. The model for investigation of the lower urinary tract showed that for low-risk patients the use of immediate cystoscopy could be avoided if cystoscopy were used for follow-up patients with a negative initial test using tumour markers and/or cytology, resulting in a saving of pounds sterling 483,000 for the evaluation of 1000 patients. The clinical and economic impact on delayed detection of both upper and lower urinary tract tumours through the use of follow-up testing should be evaluated in future studies. CONCLUSIONS: There are insufficient data currently available to derive an evidence-based algorithm of the diagnostic pathway for haematuria. A hypothetical algorithm based on the opinion and practice of clinical experts in the review team, other published algorithms and the results of economic modelling is presented in this report. This algorithm is presented, for comparative purposes, alongside current US and UK guidelines. The ideas contained in these algorithms and the specific questions outlined should form the basis of future research. Quality assessment of the diagnostic accuracy studies included in this review highlighted several areas of deficiency.

Algorithms↗

Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of urinary tract infection in children: a systematic review and economic model.

OBJECTIVES: To determine the diagnostic accuracy of tests for detecting urinary tract infection (UTI) in children under 5 years of age and to evaluate the effectiveness of tests used to investigate further children with confirmed UTI. Also, to evaluate the effectiveness of following up children with UTI and the cost-effectiveness of diagnostic and imaging tests for the diagnosis and follow-up of UTI in children under 5. An additional objective was to develop a preliminary diagnostic algorithm for healthcare professionals. DATA SOURCES: Electronic databases were searched up to the end of 2002/early 2003. Consultation with experts in the field. REVIEW METHODS: A systematic review was undertaken using published guidelines and results were analysed according to test grouping: diagnosis of UTI and further investigation of UTI. The cost-effectiveness results from existing evaluations were synthesised. A separate cost-effectiveness model was developed using the best available evidence, in part derived from the results of the systematic review, to illustrate the potential cost-effectiveness of some alternative management strategies in a UK setting. The results of the systematic review were used to propose diagnostic algorithms for the diagnosis and further investigation of UTI in children. Economic analyses did not contribute directly to the development of these algorithms. RESULTS: The studies included in the review provided very little data on the accuracy of clinical investigations for the diagnosis of UTI, and criteria for clinical suspicion of UTI were not further defined. The majority of studies included in the review found that clean voided midstream urine (CVU) samples had similar accuracy to suprapubic aspiration (SPA) samples when cultured with the advantage of being a non-invasive collection method that can be used in the GP's surgery. Pad, nappy or bag specimens may be appropriate methods for obtaining a urine sample in non-toilet-trained children, although only limited data were available. Although the glucose test was reported to have the highest accuracy in terms of both ruling in and ruling out disease, only a limited number of studies of this test were included and these were conducted over 30 years ago. Dipstick tests are easy to perform in the GP's surgery, give an immediate result and are relatively cheap. The results of the systematic review showed that a dipstick for leucocyte esterase (LE) and nitrite, where both test results are interpreted in combination, was a good test both for ruling in (both positive) and ruling out (both negative) a UTI. A dipstick positive for either LE or nitrite and negative for the other provides inconclusive diagnostic information and further testing is therefore required in these patients. Microscopy is more time consuming and expensive to perform than a dipstick test, but potentially quicker and cheaper than culture. As with dipstick tests, a combination of microscopy for pyuria and bacteriuria can be used accurately to rule in and rule out a UTI. An indeterminate test result is again obtained if microscopy is positive for either pyuria or bacteriuria, and negative for the other. Confirmatory culture is required in these patients. In patients considered to have a UTI, further culture to determine antibiotic sensitivities may be an option to inform treatment decisions. Only one study satisfied the inclusion criteria of the economic review and the review highlighted a number of potential limitations of this study for NHS decision-making. A separate decision-analytic model was therefore developed to provide a more reliable estimate of the optimal strategy regarding the diagnosis and further investigation of children under 5 with suspected UTI from the perspective of the NHS. The economic model found that the optimal diagnostic strategy for children presenting with symptoms suggestive of UTI depends on a number of key factors. These included the relevant subgroup of children concerned, in terms of gender and age, and the health service's maximum willingness to pay for an additional quality-adjusted life-year. CONCLUSIONS: The results of the systematic review were used to derive an algorithm for the diagnosis of UTI in children under 5. This algorithm represents the conclusions of the review in terms of effective practice. There were insufficient data to propose an algorithm for the further investigation of UTI in children under 5. The quality assessment highlighted several areas that could be improved upon in future diagnostic accuracy studies.

Algorithms↗

Accuracy of absence of fetal breathing movements in predicting preterm birth: a systematic review.

OBJECTIVE: To determine the accuracy with which the absence of fetal breathing movements on ultrasound examination predicts spontaneous preterm birth in women with threatened preterm labor. METHODS: Data sources included Medline, Embase, Pascal, Biosis, Cochrane Library, Medion, National Research Register, SciSearch, conference papers, and manual searching of bibliographies of known primary and review articles. A study was selected if it used absence of fetal breathing movements on ultrasound to predict spontaneous preterm birth in women with threatened preterm labor but before advanced cervical dilatation. Two reviewers independently selected studies and extracted data on their characteristics, quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables with birth within 48 h and within 7 days of testing as the reference standards. Likelihood ratios for a positive test (LR+) and negative test (LR-) were calculated as a measure of accuracy. RESULTS: There were eight studies, which included a total of 328 women, evaluating the accuracy of absence of fetal breathing movements in predicting spontaneous preterm birth in women with threatened preterm labor. There were differences in the methodological quality among the included studies. All were lacking in one or more item that make up an ideal test accuracy study. For women presenting with threatened preterm labor, meta-analysis showed a summary LR+ of 14.80 (95% CI, 6.30-34.79) with a corresponding summary LR- of 0.46 (95% CI, 0.36-0.58) for predicting preterm birth within 7 days, and summary LR+ of 7.84 (95% CI, 1.12-54.99) and summary LR- of 0.25 (95% CI, 0.13-0.48) for predicting preterm birth within 48 h of testing. CONCLUSION: Absence of fetal breathing movements has the potential to be a useful test in predicting preterm birth both within 7 days and within 48 h of testing. However, the available studies were deficient in their sample size and quality of methodology. Future research should be undertaken to evaluate this technology and to address the methodological deficiencies.

Female↗

The accuracy of risk scores in predicting preterm birth--a systematic review.

This review aims to determine the accuracy with which published risk scores predict spontaneous preterm birth in pregnant women. Studies were identified without language restrictions through nine different databases (up to June 2002), and manual searching of bibliographies of known primary and review articles. Two reviewers selected studies independently and extracted data on their characteristics, quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables of the results of risk scoring with spontaneous preterm birth as the reference standard. Heterogeneity was assessed and its reasons were explored. Summary estimates of accuracy were produced within clinically appropriate subgroups. There were 19 primary accuracy articles that met the selection criteria, including a total of 67390 women. There are 12 different risk-scoring systems, the one developed by Creasy being the most commonly evaluated. Quality features of an ideal study, such as blinding and consecutive enrolment, were frequently missing from the included studies, no study fulfilled all criteria for high quality study, and there was heterogeneity between their accuracy estimates. The reference standard most often used was birth before 37 weeks' gestation. The point estimates for the likelihood ratios (LRs) varied widely among the studies. LRs for an abnormal score (LR+) ranged from 1.0 (95% confidence interval (CI) 0.6-1.4) to 38.8 (95% CI 23.5-63.9) while that for a normal score (LR-) ranged from 0.1 (95% CI 0.02-0.6) to 1.2 (95% CI 0.9-1.6). In otherwise asymptomatic women, risk scoring in early pregnancy has a wide range of accuracy in predicting spontaneous preterm birth before 37 weeks' gestation. The evidence is of a relatively poor quality and lacks clinically important reference standards.

Female↗

Development and validation of methods for assessing the quality of diagnostic accuracy studies.

OBJECTIVES: To develop a quality assessment tool which will be used in systematic reviews to assess the quality of primary studies of diagnostic accuracy. DATA SOURCES: Electronic databases including MEDLINE, EMBASE, BIOSIS and the methodological databases of both CRD and the Cochrane Collaboration. REVIEW METHODS: Three systematic reviews were conducted to provide an evidence base for the development of the quality assessment tool. A Delphi procedure was used to develop the quality assessment tool and the information provided by the reviews was incorporated into this. A panel of nine experts in the area of diagnostic accuracy studies took part in the Delphi procedure to agree on the items to be included in the tool. Panel members were also asked to provide feedback on various other items and whether they would like to see the development of additional topic and design specific items. The Delphi procedure produced the quality assessment tool, named the QUADAS tool, which consisted of 14 items. A background document was produced describing each item included in the tool and how each of the items should be scored. RESULTS: The reviews produced 28 possible items for inclusion in the quality assessment tool. It was found that the sources of bias supported by the most empirical evidence were variation by clinical and demographic subgroups, disease prevalence/severity, partial verification bias, clinical review bias and observer/instrument variation. There was also some evidence of bias for the effects of distorted selection of participants, absent or inappropriate reference standard, differential verification bias and review bias. The evidence for the effects of other sources of bias was insufficient to draw conclusions. The third review found that only one item, the avoidance of review bias, was included in more than 75% of tools. Spectrum composition, population recruitment, absent or inappropriate reference standard and verification bias were each included in 50-75% of tools. Other items were included in less than 50% of tools. The second review found that the quality assessment tool should have the potential to be discussed narratively, reported in a tabular summary, used as recommendations for future research, used to conduct sensitivity or regression analyses and used as criteria for inclusion in the review or a primary analysis. This suggested that some distinction is needed between high- and low-quality studies. Component analysis was considered the best approach to incorporate quality into systematic reviews of diagnostic studies and this was taken into consideration when developing the tool. CONCLUSIONS: This project produced an evidence-based quality assessment tool to be used in systematic reviews of diagnostic accuracy studies. Through the various stages of the project the current lack of such a tool and the need for a systematically developed validated tool were demonstrated. Further work to validate the tool continues beyond the scope of this project. The further development of the tool by the addition of design- and topic-specific criteria is proposed.

Delphi Technique↗

Lactational amenorrhea for family planning.

BACKGROUND: 50 % of pregnancies are unwanted. For several reasons including difficulty in obtaining contraceptives, no or ineffective contraception is used to prevent these unwanted pregnancies. The Lactational Amenorrhoea Method(LAM) however is a contraceptive method available and accessible for many women. OBJECTIVES: To assess in fully breastfeeding women, staying amenorrheic, the efficacy of the Lactational Amenorrhoea Method as a contraceptive method. The efficacy of LAM, as defined in 1988 in Bellagio, was compared with alternative definitions of LAM; the outcomes were measured using pregnancy and menstruation life tables. SEARCH STRATEGY DATA SOURCES: MEDLINE searches from 1966 until 2002 and EMBASE from 1988 until 2002; reference lists of studies and review articles; books related to LAM; published abstracts from breastfeeding, reproductive health, contraceptive conferences; and e-mail communication with coordinators of such studies. SELECTION CRITERIA: From 454 potentially relevant studies 154 investigated the risk of pregnancy during LAM or lactational amenorrhea. Two reviewers applied the following inclusion criteria: prospective study, cases and -if available- controls had to be sexually active, pregnancy had to be confirmed by physical examination or a pregnancy test. Life table menstruation rates and life table pregnancy rates were taken as endpoints. Thirteen publications, reporting on 9 intervention groups and 2 control groups, met the inclusion criteria and were included in this systematic review. Their quality was assessed. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data, disagreements were resolved through discussion. Because of the heterogeneity of the included studies, the studies were analyzed using narrative methods. MAIN RESULTS: For the outcome two controlled studies of LAM users reported life table pregnancy rates at 6 months of 0.45 and 2.45 percent and 5 uncontrolled studies of LAM users reported 0-7.5 percent. Life table pregnancy rates of women fully breastfeeding and amenorrheic but not using any contraceptive method were 0.88 in one study and 0.9-1.2 percent (95% CI 0. 0-2.4 ) in a second study, depending on the definition of menstruation used. The life table menstruation rate at 6 months in all studies varied between 11.1-39.4 percent. REVIEWER'S CONCLUSIONS: No clear difference in life table pregnancy rates was found between women using LAM and supported in doing so, and fully breastfeeding, amenorroic women not using any method. Because the length of lactation amenorrhoea of women using LAM is too different between populations studied, and population specific, it is uncertain whether LAM extends lactational amenorrhoea.

Amenorrhea↗

Accuracy of cervical transvaginal sonography in predicting preterm birth: a systematic review.

This review investigates the accuracy with which transvaginal cervical sonography predicts spontaneous preterm birth. Published studies were identified without language restrictions through nine different databases and manual searching of bibliographies of known primary and review articles. Studies were selected if they undertook antenatal transvaginal sonographic cervical assessment among a population of pregnant women with known gestational age of delivery. There were 46 primary articles, which included a total of 31,577 women, consisting of 33 studies in asymptomatic and 13 studies in symptomatic women. Data were extracted for the studies' characteristics and quality. Accuracy data were used to form 2 x 2 contingency tables for various cervical length measurements with birth before 32, 34 and 37 weeks' gestation as the reference standards. Data were stratified according to singleton or twin pregnancy, gestational age at testing, cervical length threshold, and the various reference standards, and were pooled to produce summary estimates of likelihood ratios (LRs). Our review showed that transvaginal cervical sonography identifies women who are at higher risk of spontaneous preterm birth, although there was a wide variation amongst studies with respect to gestational age at testing, definition of threshold of abnormality and definition of reference standard. The most commonly reported sub-group was testing of asymptomatic women at < 20 weeks' gestation using a threshold cervical length of 25 mm with spontaneous preterm birth before 34 weeks' gestation as the reference standard. The summary LR+ for this group was 6.29 (95% CI, 3.29-12.02), with corresponding LR- of 0.79 (95% CI, 0.65-0.95). Both cervical length measurement and funneling, whether alone or in combination, appear to be useful (depending on the threshold chosen to define the abnormality) in predicting spontaneous preterm birth in asymptomatic women. For symptomatic women there was a paucity of data, although the degree of funneling appeared to be predictive of spontaneous preterm birth.

Data Collection↗

Observational studies on ultrasound screening for developmental dysplasia of the hip in newborns - a systematic review.

AIM: To assess whether observational studies provide evidence to support general ultrasound screening for developmental dysplasia of the hip (DDH). METHOD: Systematic Review. Following a predefined study protocol, observational studies on ultrasound screening in unselected newborns were identified by search through 23 electronic databases and by hand search. Two reviewers selected the studies independently of each other and extracted the data. RESULTS: 49 observational studies were included. The prevalence of DDH ranged from 0.5 % to 30 % depending largely on the various possible definitions of DDH. Less than 0.1 % of patients with DDH were missed by ultrasound regardless of the technique employed (Graf or Terjesen). About 90 % of newborns with Graf type IIa hips requiring ultrasound control did not develop DDH. Only six studies with 23 108 newborns reported on complications, and there was only one infant with an avascular necrosis of the femoral head. The effectiveness of a general ultrasound screening cannot be evaluated reliably for several reasons: reports were often incomplete, follow-up of newborns with normal findings at the time of screening was often not carried out, clinically meaningful data about outcome as well as control groups were missing. CONCLUSION: General ultrasound screening for developmental dysplasia of the hip cannot be sufficiently assessed by the observational studies available. The lack of evidence does not mean that ultrasound screening is ineffective, but randomized controlled trials comparing the effectiveness of different screening regimens are needed.

Costs and Cost Analysis↗

The York review--a systematic review of public water fluoridation: a commentary.

Following the election of the British government in May 1997, a policy document outlining proposals to improve the health of the nation was published. This document placed a major emphasis on reducing inequalities in health and recognised the continuing poor state of oral health in deprived communities. However, whilst acknowledging the benefits of water fluoridation as a caries preventive measure, the Department of Health suggested that most of the research had been carried out some years ago and furthermore, recognised that strong views were held both for and against fluoridation.

Cariostatic Agents↗

Acupuncture.

Explore the source record for details and available documents.

Acupuncture↗

Homoeopathy.

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Drug Prescriptions↗

Quality of Cochrane reviews: assessment of sample from 1998.

OBJECTIVE: To assess the quality of Cochrane reviews. DESIGN: Ten methodologists affiliated with the Cochrane Collaboration independently examined, in a semistructured way, the quality of reviews first published in 1998. Each review was assessed by two people; if one of them noted any major problems, they agreed on a common assessment. Predominant types of problem were categorised. SETTING: Cyberspace collaboration coordinated from the Nordic Cochrane Centre. STUDIES: All 53 reviews first published in issue 4 of the Cochrane Library in 1998. MAIN OUTCOME MEASURE: Proportion of reviews with various types of major problem. RESULTS: No problems or only minor ones were found in most reviews. Major problems were identified in 15 reviews (29%). The evidence did not fully support the conclusion in nine reviews (17%), the conduct or reporting was unsatisfactory in 12 reviews (23%), and stylistic problems were identified in 12 reviews (23%). The problematic conclusions all gave too favourable a picture of the experimental intervention. CONCLUSIONS: Cochrane reviews have previously been shown to be of higher quality and less biased on average than other systematic reviews, but improvement is always possible. The Cochrane Collaboration has taken steps to improve editorial processes and the quality of its reviews. Meanwhile, the Cochrane Library remains a key source of evidence about the effects of healthcare interventions. Its users should interpret reviews cautiously, particularly those with conclusions favouring experimental interventions and those with many typographical errors.

Bias↗

Association of Down's syndrome and water fluoride level: a systematic review of the evidence.

BACKGROUND: A review of the safety and efficacy of drinking water fluoridation was commissioned by the UK Department of Health to investigate whether the evidence supported a beneficial effect of water fluoridation and whether there was any evidence of adverse effects. Down's syndrome was one of the adverse effects reported. The aim of this review is to examine the evidence for an association between water fluoride level and Down's syndrome. METHODS: A systematic review of research. Studies were identified through a comprehensive literature search, scanning citations and online requests for papers. Studies in all languages which investigated the incidence of Down's syndrome in areas with different levels of fluoride in their water supplies were included. Study inclusion and quality was assessed independently by 2 reviewers. A qualitative analysis was conducted. RESULTS: Six studies were included. All were ecological in design and scored poorly on the validity assessment. The estimates of the crude relative risk ranged from 0.84 to 3.0. Four studies showed no significant associations between the incidence of Down's syndrome and water fluoride level and two studies by the same author found a significant (p < 0.05) positive association (increased Down's syndrome incidence with increased water fluoride level). Only two of the studies controlled for confounding factors and only one of these presented summary outcome measures. CONCLUSIONS: The evidence of an association between water fluoride level and Down's syndrome incidence is inconclusive.

Consumer Product Safety↗