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Analysis of repeated measurements with dropouts among Alzheimer's disease patients using summary measures and meta-analysis.

A method of stratifying the data according to the patterns of missing observations, summarizing each subject's repeated measurements by a summary measure and then comparing the treatment groups with the help of a distribution-free test based on the summary measure, is used here to compare the efficacy of tacrine dose regimens with that of placebo in a recent trial in Alzheimer's disease patients. The usefulness of the method of meta-analysis for comparing the treatment groups, in the presence of missing data, is also investigated.

Alzheimer Disease↗

Is tubal embryo transfer of any value? A meta-analysis and comparison with the Society for Assisted Reproductive Technology database.

OBJECTIVE: To analyze published randomized trials of ZIFT and ET via meta-analysis and compare the results with those of the Society for Assisted Reproductive Technology database. DESIGN: Meta-analysis and comparison to SART data sets for 1991-1996. SETTING: University medical center. PATIENT(S): Patients from the literature with infertility, randomized to either tubal or uterine embryo transfer. INTERVENTION(S): All published articles in English were identified using an electronic database spanning January 1966 to December 1998 by keyword and text word searches, supplemented with a hand search through the references of original studies, review articles, and conference abstracts to identify randomized trials comparing ZIFT and IVF-ET. Additional data was obtained through correspondence with authors. MAIN OUTCOME MEASURE(S): Implantation and clinical pregnancy rates were compared. Ectopic pregnancy rate was a secondary outcome measure. RESULT(S): Six randomized controlled trials including 548 cycles, 514 retrievals, and 388 transfers were reviewed. Demographic and stimulation and transfer details were comparable between the groups. Implantation and pregnancy rates did not differ significantly, and there was a trend toward increased risk of ectopic pregnancy with ZIFT. CONCLUSION(S): Published randomized trials suggest that there is no difference in implantation and pregnancy rates between women undergoing ZIFT and IVF-ET.

Databases, Factual↗

Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass.

UNLABELLED: Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. INTRODUCTION: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. MATERIALS AND METHODS: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. RESULTS: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. CONCLUSIONS: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance.

Bone Density↗

Alcohol consumption and the risk of cancer: a meta-analysis.

Alcohol consumption has been linked to an increased risk for various types of cancer. A combined analysis of more than 200 studies assessing the link between alcohol and various types of cancer (i.e., a meta-analysis) sought to investigate this association in more detail. This meta-analysis found that alcohol most strongly increased the risks for cancers of the oral cavity, pharynx, esophagus, and larynx. Statistically significant increases in risk also existed for cancers of the stomach, colon, rectum, liver, female breast, and ovaries. Several mechanisms have been postulated through which alcohol may contribute to an increased risk of cancer. Concurrent tobacco use, which is common among drinkers, enhances alcohol's effects on the risk for cancers of the upper digestive and respiratory tract. The analysis did not identify a threshold level of alcohol consumption below which no increased risk for cancer was evident.

Alcohol Drinking↗

Meta-analysis of the clinical outcome of carbapenem monotherapy in the adjunctive treatment of intra-abdominal infections.

BACKGROUND: The carbapenems, a class of beta-lactam antimicrobials with efficacy against both aerobic and anaerobic organisms, have demonstrated potential as monotherapeutic regimens in the treatment of serious intra-abdominal infections. Clinical trials have been conducted in the past decade to compare carbapenem monotherapy versus combinations of antibiotic therapy. We report here a meta-analysis of 10 such trials. DATA SOURCES: An 11-year Medline search (from 1985 through 1996) of the English-language literature identified clinical trials that compared the outcomes of carbapenem monotherapy, either imipenem/cilastatin or meropenem, versus another antibiotic regimen in intra-abdominal infections in human subjects. Ten randomized, prospective trials were found, with a total of 1,227 clinically evaluable patients. A meta-analysis of these clinical trials was performed to determine the difference in clinical outcomes between carbapenem monotherapy versus other antibiotic regimens. We found a difference in response rates of -1.6% (95% confidence interval [CI] -5.7% to 2.5%) and a response ratio of 0.99 (95% CI, 0.90 to 1.09), indicating no statistical significant difference. CONCLUSIONS: A meta-analysis of 10 clinical trials from 1985 through 1996 has revealed no statistical significant difference in clinical response between carbapenem monotherapy and combinations of antibiotic therapy in intra-abdominal infections. We noted, however, that the earlier studies reported more favorable response ratios for carbapenems than later publications. This may have been due to the selection of less effective comparators in earlier studies. We conclude that carbapenem monotherapy is as effective as combinations of antimicrobials for the treatment of intra-abdominal infections.

Abdomen↗

Meta-analysis of prostacyclin therapy for persistent pulmonary hypertension with congenital diaphragmatic hernia.

OBJECTIVE: To evaluate the efficacy and safety of prostacyclin in the treatment of persistent pulmonary hypertension in congenital diaphragmatic hernia. METHODS: A systematic literature search was conducted in four main databases (PubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The protocol was registered in advance in the International Prospective of Systematic Reviews (CRD420261325458). RESULTS: A total of nine studies were included involving a total of 7009 infants in this systematic review and meta-analysis. GRADE assessment revealed substantial heterogeneity in the quality of evidence across outcomes, with most outcomes rated very low quality and only one rated moderate quality. Studies were performed meta-analysis, which showed the use of prostacylin resulted a statistically significant decrease in the OI compared to the control group (Mean Difference (MD), 9.34; I2 0%; p < 0.00001), no statistically significant in mortality (OR, 0.83; I2 84%; p = 0.70), ECMO (OR = 4.9; I2 98%; p = 0.27), BNP (std MD, 6.98; I2 98%; p = 0.31), FiO2 (SMD = 8.0;, I2 64%; p = 0.11), Systolic orientation of IVS curvature (SMD = 0.69; I2 97%; p = 0.32), Diastolic orientation of IVS differences (MD = 0.62; I2 93% p = 0.26). After applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. CONCLUSION: In conclusion, this meta-analysis has confirmed that prostacyclin may temporarily improve oxygenation. However, after applying the Hartung-Knapp adjustment, with the exception of BNP, the pooled effects of the other outcomes were not statistically significant, and there was high heterogeneity in measures such as ECMO and ventricular septal curvature. Further validation through high-quality studies are still needed. TRIAL REGISTRATION: PROSPERO: CRD420261325458.

Humans↗

Inhaled corticosteroids reduce the progression of airflow limitation in chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a syndrome of chronic progressive airflow limitation which occurs as a result of chronic inflammation of the airways and lung parenchyma. However, the role of inhaled corticosteroids in the treatment of COPD is controversial. We hypothesised that inhaled corticosteroids reduce the progression of airflow limitation in COPD. METHODS: A comprehensive literature search was conducted and data were analysed using random effects methodology. The effect of inhaled steroids on annual change in forced expiratory volume in 1 second (FEV1) was determined for all trials, for trials with high dose treatment regimens, and for trials in subjects with moderate to severe airflow limitation. RESULTS: Data from eight controlled clinical trials of > or =2 years were included (n=3715 subjects). Meta-analysis of all study data revealed that inhaled corticosteroids reduce the rate of FEV1 decline by 7.7 ml/year (95% confidence interval (CI) 1.3 to 14.2, p=0.02). Meta-analysis of studies with high dose regimens revealed a greater effect of 9.9 ml/year (95% CI 2.3 to 17.5, p=0.01) compared with the meta-analysis of all studies. CONCLUSIONS: Inhaled corticosteroid treatment for > or =2 years slows the rate of lung function decline in COPD. The effect observed with high dose regimens is greater than that with all regimens combined. These data suggest a potential role for inhaled corticosteroids in modifying the long term natural history of COPD.

Administration, Inhalation↗

The value of FDG-PET in the detection, grading and response to therapy of soft tissue and bone sarcomas; a systematic review and meta-analysis.

BACKGROUND: Sarcomas represent a significant diagnostic and therapeutic challenge that requires techniques to provide better assessment of the disease than provided by traditional means. FDG-PET depicts the increased metabolism in abnormal tissues, enabling visualisation and quantification in vivo. The objective of this review was to assess the diagnostic value of FDG-PET in the detection, grading and therapy response of soft tissue and bone sarcomas. METHODS: A systematic review and meta-analysis of clinical studies on FDG-PET and sarcomas was conducted. Databases of PubMed, Embase and Cochrane were searched for studies. Besides that, the references of identified studies were reviewed. Three reviewers independently assessed the methodological quality. Statistical pooling was possible for studies concerning detection and grading of studies with mixed sarcomas (soft tissue and bone) and studies with soft tissue sarcomas only. RESULTS: Twenty-nine studies met the inclusion criteria. There was disagreement between the reviewers in 21.5% of the questions from the criteria list. The methodological quality of most of the included studies was poor. Pooled sensitivity, specificity and accuracy of PET for the detection of sarcomas were 0.91, 0.85 and 0.88, respectively. The difference between the mean Standard Uptake Value (SUV) in malignant and benign tumours for the studies concerning mixed and soft tissue sarcomas was statistically significant, as well as the difference in FDG uptake between low and high grade mixed sarcomas. CONCLUSIONS: The meta-analysis in this study was limited by the fact that only a few studies had mutual comparable outcome parameters. Moreover, the methodological quality of the studies was generally poor. Nevertheless, our results indicate that FDG-PET can discriminate between sarcomas and benign tumours and low and high grade sarcomas based on the mean SUV. The diagnostic implications of these results have to be investigated, especially the discrimination between benign tumours and low grade sarcomas. Based on this meta-analysis, there is no indication to use FDG-PET in the standard treatment of sarcomas. In the future PET imaging in bone and soft tissue sarcomas should be directed to the clinical implication for the detection and grading of sarcomas and the treatment evaluation of locally advanced sarcomas.

Adolescent↗

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD&#xa0;=&#xa0;-0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD&#xa0;=&#xa0;-0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans↗

Assessing the neonatal safety of indomethacin tocolysis: a systematic review with meta-analysis.

OBJECTIVE: To systematically review and summarize the medical literature regarding the effects of tocolysis with indomethacin on neonatal outcome. DATA SOURCES: We supplemented a search of entries in electronic databases with references cited in original studies and review articles to identify studies pertaining to indomethacin tocolysis and neonatal outcome. METHODS OF STUDY SELECTION: We evaluated, abstracted data, and performed quantitative analyses in studies assessing the neonatal outcomes of patients undergoing tocolysis with indomethacin. Observational studies and randomized trials were included in this systematic review. TABULATION, INTEGRATION, AND RESULTS: Forty-six studies were identified, 28 of which met criteria for systematic review and meta-analysis. These 28 studies included 6,008 infants. Of these infants, 1,621 were exposed to indomethacin for tocolysis antenatally; 4,387 infants not exposed to indomethacin served as the comparison group. An estimate of pooled odds ratios with 95% confidence intervals was calculated for dichotomous outcomes using random- and fixed-effects models. Observational studies and randomized trials were analyzed separately. Pooled estimates from observational studies and randomized trials revealed no significant differences in the rates of intraventricular hemorrhage, patent ductus arteriosus, necrotizing enterocolitis, or neonatal mortality between infants exposed to indomethacin antenatally and those not exposed. Meta-analysis of randomized trials revealed increased risk of bronchopulmonary dysplasia. However, the meta-analysis included only 3 randomized clinical trials, one of which showed increased risk. An association of bronchopulmonary dysplasia and indomethacin use was not noted in our analysis of observational studies. CONCLUSION: Although our pooled results did not identify significantly increased risks of adverse effects, the limited statistical power of published randomized trials does not allow us to exclude the possibility that indomethacin tocolysis increases the risk of adverse neonatal outcomes.

Adult↗

Meta-analysis of randomized trials comparing off-pump with on-pump coronary artery bypass graft patency.

BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCAB) is increasingly becoming a widely used technique and challenges conventional on-pump coronary artery bypass grafting as the standard surgical therapy for coronary artery disease. Little information, however, is available concerning postoperative performance of bypass grafts done with this new technique. The aim of this study is to assess differences in graft patency between OPCAB and coronary artery bypass grafting by meta-analysis of data published in randomized trials. METHODS: A literature search for the period beginning January 1990 until December 2004 supplemented with manual bibliographic review was performed for all peer-reviewed English-language publications. A systematic overview (meta-analysis) of randomized trials was conducted to assess differences between OPCAB and coronary artery bypass grafting in graft occlusion rates. RESULTS: Literature search yielded five comparable randomized studies, for a total of 872 and 998 grafts performed during OPCAB and coronary artery bypass grafting procedures, respectively. Meta-analysis of these studies showed an increased risk of graft occlusion in the OPCAB group of patients, both when all the studies were analyzed together (odds ratio, 1.51; 95% confidence intervals, 1.15 to 1.99; p = 0.003), and when low-quality (odds ratio, 1.46; 95% confidence intervals, 1.05 to 2.03; p = 0.02) and high-quality (odds ratio, 1.65; 95% confidence intervals, 0.99 to 2.75; p = 0.05) studies were analyzed separately. CONCLUSIONS: Cumulative analysis of the few prospective randomized studies currently available in the literature documents a reduction in postoperative patency of coronary artery bypass grafts performed during OPCAB procedures. The risk of reduced graft patency needs to be considered when choosing OPCAB as tailored strategy for selected patients.

Coronary Artery Bypass↗

Comparison of the efficacy of cooled-tip and 8-mm-tip catheters for radiofrequency catheter ablation of the cavotricuspid isthmus: a meta-analysis.

BACKGROUND: Cooled-tip RFA (cRFA) and conventional 8-mm-tip catheters were found to be more effective and as safe as conventional 4-mm-tip catheters for atrial flutter (AFL) radiofrequency ablation (RFA), facilitating the rapid achievement of bi-directional isthmus block (BIB), but studies comparing cRFA and 8-mm-tip catheters are not randomized or results are discussed. Thus, we performed a meta-analysis of available randomized trials to evaluate the effectiveness in terms of primary success and procedure parameters. METHODS: Reports of trials were identified through a Medline, Embase, Current Contents, Cardline, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, and open trials; (2) patients assigned to an 8-mm-tip or a cRFA catheter for AFL RFA; (3) endpoints events related to primary success rate (BIB achievement), and procedure parameters (number of RF applications, x-ray exposure and ablation duration). RESULTS: Seven trials met the inclusion criteria. They included 603 patients with established AFL randomized to an 8-mm-tip or cRFA catheter group. Comparing 8-mm groups with cRFA groups, the meta-analysis showed similar BIB achievement relative risk (RR) 0.96, 95% confidence interval (CI): 0.92 to 1.01, (P = 0.13); total RF application time weighted mean difference (WMD) 0.88, 95% CI: -0.36 to 2.12, (P = 0.16); duration of x-ray exposure (min) (WMD = 1.07, 95% CI: -0.81 to 0.295, (P = 0.26); ablation procedure duration (min) (WMD = 0.68, 95% CI: -3.37 to 4.73; P = 0.74). CONCLUSION: The present meta-analysis confirms that cooled-tip and large-tip catheters are equally efficient for cavotricuspid isthmus ablation with both similar primary success rates and procedure parameters.

Aged↗

An individual patient data meta-analysis of long supported adjuvant chemotherapy with oral carmofur in patients with curatively resected colorectal cancer.

To reappraise the benefits of the long supported chemotherapy with carmofur, a meta-analysis based on individual patient data from the three clinical trials was performed by pooling 614 patients from three trials, there is a statistically significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit (2p=0.021) for carmofur; and a highly significant advantage for carmofur in DFS (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta-analysis strongly suggested an effect of oral carmofur in a long supported chemotherapy for curatively resected colorectal carcinoma.

Administration, Oral↗

Behavioral and prophylactic pharmacological intervention studies of pediatric migraine: an exploratory meta-analysis.

In this review, the effectiveness of behavioral and pharmacological treatments for pediatric migraine was quantitatively summarized following the meta-analytic approach outlined by Hedges and Olkin (1985). A first meta-analysis based on treatment outcome within treatment conditions revealed that thermal biofeedback and interventions combining biofeedback and progressive muscle relaxation seem to be significantly more efficacious than other behavioral treatment modalities, psychological and drug placebo, and the more commonly used prophylactic drug regimens. Though there is some evidence suggesting good effectiveness of propranolol, the lack of systematic data precludes more definitive conclusions. A second meta-analysis that included only studies providing data on the comparison between control versus active treatment conditions replicated the initial findings only partially. In the light of the relative small number of studies that met basic inclusion requirements, the methodological flaws of many studies, and the under-representation of certain treatment types, conclusions regarding differential effectiveness of the treatment types have to be drawn with caution. Overall, our findings clearly demonstrate the need for direct comparisons between behavioral and pharmacological treatments and the need for more theory-driven research in order to determine the most promising treatment approaches for pediatric migraine.

Behavioral Medicine↗

Time-dependent surgical outcomes following cauda equina syndrome diagnosis: comments on a meta-analysis.

STUDY DESIGN: In this Journal Club review, we critically examine the methodology and results of a recently published meta-analysis describing the time dependency of surgical outcomes associated with cauda equina syndrome (CES) diagnosis. OBJECTIVES: Our objectives are to clarify the strengths, weaknesses, and appropriate use of statistics regarding the findings of the previous publication. SUMMARY OF BACKGROUND DATA: Surgical outcomes from published reports are related to both preoperative conditions and the time between surgery and diagnosis of CES. METHODS: We reexamined many of the papers that were used to create the surgical outcomes data set, including the publications that supplied quantitative information for logistic regression. Of special focus were studies that contributed to the "less than 24 hours from diagnosis" data. The use of statistical parameters such as probabilities and odds ratios to infer possible future outcomes is also addressed to clarify the papers' interpretations. To support the overall limitations of their generalized findings, we conducted a power analysis, which highlights the lack of statistical strength in the resulting conclusions. RESULTS: The results of the initial work state that an advantage exists in treating patients within 48 hours in comparison to treating them during a period greater than 48 hours after the onset of CES symptoms. However, the authors also state that no difference exists between the effects of an early surgery (less than 24 hours) compared with a subsequent period between 24 and 48 hours after CES onset. Key elements of logistic regression and meta-analysis are used to refute specific aspects of their methodology as well as their clinical interpretation regarding acute intervention. CONCLUSIONS: We conclude that a flawed methodology and misinterpretation of results are reported, understating the value of early surgical intervention.

Humans↗

How useful are unpublished data from the Food and Drug Administration in meta-analysis?

The goals of this systematic review and meta-analysis were to ascertain whether studies of nonsteroidal anti-inflammatory drugs (NSAIDs) summarized in the FDA reviews are ultimately published, to compare the methodologic and population characteristics of studies summarized in the FDA reviews with those reported in peer reviewed literature, and to compare the pooled relative risk of dyspepsia from NSAIDs in each data source. Summary measures of risk difference were calculated with a random effects model; meta-regression was used to assess the effect of study covariates. Among 37 studies described in the FDA reviews, one was published. Sample size, gender distribution, indication for drug use, and methodologic quality did not vary significantly between the published and FDA data. The pooled risk ratio for dyspepsia obtained using published data (1.21) or FDA data (1.07) did not differ significantly or practically. Data from FDA reviews may be a viable data source for systematic reviews and meta-analyses but only after being subjected to the same methodologic scrutiny as published data.

Adult↗

Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials.

BACKGROUND: The effect of fish oil on heart rate (HR), a major risk factor for sudden death, is not well established. We calculated this effect in a meta-analysis of randomized, double-blind, placebo-controlled trials in humans. METHODS AND RESULTS: Randomized trials of fish oil that evaluated HR were identified through MEDLINE (1966 through January 2005), hand-searching of references, and contact with investigators for unpublished results. Two investigators independently extracted trial data. A pooled estimate was calculated from random-effects meta-analysis. Predefined stratified meta-analyses and meta-regression were used to explore potential heterogeneity. Of 197 identified articles, 30 met inclusion criteria. Evidence for publication bias was not present. In the overall pooled estimate, fish oil decreased HR by 1.6 bpm (95% CI, 0.6 to 2.5; P=0.002) compared with placebo. Between-trial heterogeneity was evident (Q test, P<0.001). Fish oil reduced HR by 2.5 bpm (P<0.001) in trials with baseline HR > or =69 bpm (median) but had little effect (0.04-bpm reduction; P=0.56) in trials with baseline HR <69 bpm (P for interaction=0.03). Fish oil reduced HR by 2.5 bpm (P<0.001) in trials with duration > or =12 weeks but had less effect (0.7-bpm reduction; P=0.27) in trials with duration <12 weeks (P for interaction=0.07). HR reduction with fish oil intake did not significantly vary by fish oil dose (range, 0.81 to 15 g/d), type of HR measure, population age, population health, parallel versus crossover design, type of control oil, or study quality by Delphi criteria (P for interaction >0.25 for each). CONCLUSIONS: In randomized controlled trials in humans, fish oil reduces HR, particularly in those with higher baseline HR or longer treatment duration. These findings provide firm evidence that fish oil consumption directly or indirectly affects cardiac electrophysiology in humans. Potential mechanisms such as effects on the sinus node, ventricular efficiency, or autonomic function deserve further investigation.

Adult↗

HPV testing and monitoring of women after treatment of CIN 3: review of the literature and meta-analysis.

According to the current guidelines in most western countries, women treated for cervical intraepithelial neoplasia grade 3 (CIN 3) are followed for at least 2 years after treatment by cytology.High-risk human papillomavirus (hrHPV) infections are necessary for the development and maintenance of CIN 3. HrHPV testing could be used to improve monitoring of women treated for CIN 3. This has prompted numerous studies for the implementation of hrHPV testing in monitoring of women treated for CIN 3. Included in this review are 20 studies, published between 1996 and 2003, comparing hrHPV testing with either resection margins or cervical cytology to predict recurrent/residual disease, and 11 of them could be used in a meta-analysis. In the meta-analysis of the 11 studies, the negative predictive value (NPV) for recurrent/residual disease of hrHPV testing was 98% (95% CI 97-99%), that of resection margins 91% (95% CI 87-94%), and that of cervical cytology 93% (95% CI 90-95%). When hrHPV testing was performed in conjunction with cytology, the sensitivity was 96% (95% CI 89-99%), specificity was 81% (95% CI 77-84%), the associated positive predictive value (PPV) was 46% (95% CI 38-54%), and the NPV was 99% (95% CI 98-100%). Combined hrHPV and cytology testing yielded the best test characteristics. We propose to include hrHPV testing in conjunction with cytology for monitoring women treated for CIN 3. Some follow-up visits for women testing negative for both hrHPV and cytology can be skipped. In western countries, this could mean that for women double negative at 6 months, retesting at 12 months should be skipped while keeping the 24-month follow-up visit.

Cervix Uteri↗