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[A meta-analysis of randomized controlled trials of tianeptine versus SSRI in the short-term treatment of depression].

A meta-analysis was performed to compare the efficacy of tianeptine and selective serotonin reuptake inhi-bitors (SSRI) in the short-term treatment of depression. Consecutive selection and inclusion processes allowed five stu-dies to be selected: two studies on tianeptine versus fluoxetine, two studies on tianeptine versus paroxetine, and one study on tianeptine versus sertraline. A total of 1 348 patients were included in the five studies; 681 subjects received an SSRI and 667 tianeptine. A strict step-by-step methodology was applied in order to legitimize this meta-analysis and to interpret the results. Considering all the patients or those with a Montgomery-Asberg Depression Rating Scale (MADRS) inclusion score greater or equal than 28, none of the assessed parameters (MADRS total score and responder rate) revealed any significant difference between the two treatment groups. Further analysis based on clinical global impression (CGI) items found no significant difference, except for CGI item 3 (therapeutic index), where a tendency (p=0.06 or 0.07 depending on the methodology) was found in favor of tianeptine. All in all, this study confirmed that tianeptine is at least as effective as SSRI, with a trend for a better acceptability profile in the treatment of depressed patients.

Antidepressive Agents, Tricyclic↗

Achieving 2003 European lipid goals with rosuvastatin and comparator statins in 6743 patients in real-life clinical practice: DISCOVERY meta-analysis.

BACKGROUND: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals. OBJECTIVE: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice. RESULTS: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10 mg achieved the 2003 European LDL-C goals compared with those who received atorvastatin 10 mg or simvastatin 20 mg (p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10 mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10 mg (p < 0.001). CONCLUSIONS: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL-C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.

Aged↗

Generous-like flowers: nectar production in two epiphytic bromeliads and a meta-analysis of removal effects.

Animal-pollinated angiosperm plants that respond positively to nectar removal by replenishment invest energy that can entail a reproductive cost. We investigated whether or not nectar removal stimulates replenishment in two hummingbird-pollinated bromeliad species. Nectar replenishment rates were also assessed by removing nectar from manually pollinated flowers because pollination events might be used as signals to save energy by preventing allocation to post-pollination nectar production. Then we synthesized the current understanding of nectar removal effects by reviewing existing published studies with a meta-analysis. The magnitude and significance of estimated nectar removal effects and factors associated with variation in size and direction of nectar removal effects were elucidated with the meta-analysis. We found that both Tillandsia species strongly respond to repeated nectar removal by producing >3 times additional nectar. Nectar secretion patterns were not altered by pollination (stigmatic pollen deposition) and we found no evidence of nectar reabsorption. Although the effect size varied widely across systems and/or environmental conditions, the meta-analysis showed that nectar removal had overall a positive effect on nectar replenishment (mainly among species inhabiting wet tropical habitats such as Tillandsia), and a negative effect on the secretion of additional sugar, suggesting that those plants are resource limited and conservative in the secretion of additional sugar.

Adaptation, Physiological↗

A meta-analysis of the training effectiveness of virtual reality surgical simulators.

The increasing use of virtual reality (VR) simulators in surgical training makes it imperative that definitive studies be performed to assess their training effectiveness. Indeed, in this paper we report the meta-analysis of the efficacy of virtual reality simulators in: 1) the transference of skills from the simulator training environment to the operating room, and 2) their ability to discriminate between the experience levels of their users. The task completion time and the error score were the two study outcomes collated and analyzed in this meta-analysis. Sixteen studies were identified from a computer-based literature search (1996-2004). The meta-analysis of the random effects model (because of the heterogeneity of the data) revealed that training on virtual reality simulators did lessen the time taken to complete a given surgical task as well as clearly differentiate between the experienced and the novice trainees. Meta-analytic studies such as the one reported here would be very helpful in the planning and setting up of surgical training programs and for the establishment of reference 'learning curves' for a specific simulator and surgical task. If any such programs already exist, they can then indicate the improvements to be made in the simulator used, such as providing for more variety in their case scenarios based on the state and/or rate of learning of the trainee.

Computer Simulation↗

Association between anaemia and osteoporosis: a systematic review and meta-analysis.

BACKGROUND: Osteoporosis significantly impacts global morbidity. Recent evidence suggests anaemia may contribute to osteoporosis risk. This systematic review and meta-analysis investigates this association. METHODS: PubMed, Scopus, EBSCO, and ScienceDirect were searched for papers. Studies with definition of anaemia and assessing osteoporosis outcomes were included. Meta-analysis utilized random-effects models (DerSimonian-Laird method), and study quality was assessed via Newcastle-Ottawa Scale (NOS). Analyses were performed using R Studio. RESULT: Eighteen studies (861,540 participants) were analyzed. Anaemia significantly increased osteoporosis risk in univariate analysis (OR 1.62; 95% CI 1.33-1.98; p&#x2009;<&#x2009;0.001), despite high heterogeneity (I2 = 92.7%). The results remain significant in studies that reported multivariate analysis (OR 2.01; 95% CI 1.26-3.21; p&#x2009;=&#x2009;0.004). Sensitivity analyses confirmed the robustness of our result. CONCLUSION: Anaemia significantly associated with osteoporosis, emphasizing the need for targeted screening in anaemic individuals. Further studies should consider incorporating anaemia into osteoporosis and fracture prediction tools.

Humans↗

Identification of chromosomal regions linked to premature myocardial infarction: a meta-analysis of whole-genome searches.

Myocardial infarction (MI) is a complication of coronary artery disease and the leading cause of death in the Western world. MI is considered a distinct phenotype with an increased genetic component for its premature type. MI's exact inheritance pattern is still unknown. Genome searches for identifying susceptibility loci for premature MI produced inconclusive or inconsistent results. Thus, a genome search meta-analysis (GSMA) was applied to available genome search data on premature MI. GSMA is a non-parametric method to identify genetic regions that rank high, on average in terms of linkage statistics across genome searches unweighted or weighted by study size. The significance of each region's average and heterogeneity, unadjusted or adjusted by neighbouring average simulated ranks, was calculated using a Monte Carlo test. The meta-analysis involved five genome searches in Caucasians. Eight regions (6p22.3-6p21.1, 14p13-14q13.1, 13q33.1-13q34, 5p15.33-5p15.1, 8q13.2-8q22.2, 1p36.21-1p35.2, 12q24.31-12q24.33, 8q24.21-8q24.3) were found to have significant average rank by either unweighted or weighted analyses. In addition, region 8q24.21-8q24.3 produced significant low heterogeneity (P (unadjusted)=0.03 and P (adjusted)=0.05). Four regions (6p22.3-6p21.1, 14p13-14q13.1, 8q13.2-8q22.2, 8q24.21-8q24.3) were not identified by the individual studies. The meta-analysis suggests that these four regions should be further investigated for genes that confer susceptibility to MI.

Adult↗

Interleukin 6 -174 g/c promoter polymorphism and risk of coronary heart disease: results from the rotterdam study and a meta-analysis.

OBJECTIVE: Inflammation plays a pivotal role in the pathogenesis of atherosclerosis. Interleukin (IL) 6 has many inflammatory functions, and the IL-6 -174 G/C promoter polymorphism appears to influence IL-6 levels. Findings of previous studies on the relation between this polymorphism and risk of cardiovascular diseases are inconsistent. We investigated this polymorphism in relation to risk of coronary heart disease (CHD) in a population-based study and meta-analysis. METHODS AND RESULTS: Participants (6434) of the Rotterdam Study were genotyped. Analyses on the relation between genotype and CHD were performed using Cox proportional hazards tests, and the association between genotype and plasma levels of IL-6 and C-reactive protein was investigated. All of the analyses were adjusted for age, sex, and common cardiovascular risk factors. A meta-analysis was performed, using a random effects model. No association between genotype and risk of CHD was observed. The polymorphism was not associated with IL-6 levels, but the C-allele was associated with higher C-reactive protein levels (P<0.01). Our meta-analysis did not show a significant association between the genotype and risk of CHD. CONCLUSIONS: We conclude that the polymorphism is not a suitable genetic marker for increased risk of CHD in subjects > or =55 years of age.

Aged↗

Follow-up of colorectal cancer: a meta-analysis.

PURPOSE: The value of intensive follow-up for patients after resection of colorectal cancer remains controversial. This study reviews all randomized and prospective cohort studies to assess the value of aggressive follow-up. METHODS: The literature was searched from the years 1972 to 1996 for studies reporting on the follow-up of patients with colorectal cancer. Randomized and comparative-cohort studies that included history, physical examination, and carcinoembrionic antigen values at least three times a year for at least two years were included in a meta-analysis. Single-cohort studies with intensive follow-up and traditional follow-up were also included in a two-group comparative analysis for each outcome indicator. Outcome indicators were 1) curative resection rates after recurrent cancer, 2) survival rates of curative re-resections, 3) length of survival after recurrence, and 4) cumulative five-year survival. RESULTS: Two randomized and three comparative-cohort studies met these criteria and included 2,005 patients, which were evaluated in the meta-analysis. The cumulative five-year survival was 1.16 times higher in the intensively followed group (P = 0.003). Two and one-half times more curative re-resections were performed for recurrent cancer in those patients undergoing intensive follow-up (P = 0.0001). Those patients in the intensive follow-up group with a recurrence had a 3.62-times higher survival rate than the control (P = 0.0004). Fourteen single-cohort studies were also included in the comparative analysis of 6,641 patients. The findings from these aggregated studies support the results of the meta-analysis. CONCLUSION: Our study concludes that intensive follow-up detects more recurrent cancers at a stage amenable to curative resection, resulting in an improvement in survival of recurrences and an increased overall five-year cumulative rate of survival.

Adult↗

Safety of metronidazole in pregnancy: a meta-analysis.

OBJECTIVE: Our purpose was to determine from published experience in humans whether metronidazole exposure during the first trimester of pregnancy is associated with an increased teratogenic risk. STUDY DESIGN: All published articles reporting on metronidazole use during pregnancy were screened by two independent reviewers to select those including pregnant patients exposed during the first trimester and comparing the outcomes of their pregnancies with that of patients either not exposed to metronidazole or exposed only during the third trimester. The outcome under consideration was the occurrence of birth defects in live-born infants. The overall odds ratios of first-trimester exposure versus no first-trimester exposure was calculated by combining the selected studies in a meta-analysis according to the procedure of Mantel and Haenszel. RESULTS: From 32 identified studies, 7 met the inclusion criteria for meta-analysis. Six were prospective and included 253 women exposed to the drug in the first trimester of pregnancy; one was retrospective and reported on 1083 exposed women. The overall weighted odds ratio of exposure versus no exposure during the first trimester calculated by meta-analysis of the 7 studies was 0.93 (95% confidence interval 0.73 to 1.18). The odds ratio calculated from the 6 prospective studies was 1.02 (95% confidence interval 0.48 to 2.18). CONCLUSION: Metronidazole does not appear to be associated with an increased teratogenic risk.

Abnormalities, Drug-Induced↗

Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis.

PURPOSE: The modulation of fluorouracil (FU) by folinic acid (leucovorin [LV]) has been shown to be effective in terms of tumor response rate in patients with advanced colorectal cancer, but a meta-analysis of nine trials previously published by our group failed to demonstrate a statistically significant survival difference between FU and FU-LV. We present an update of the meta-analysis, with a longer follow-up and the inclusion of 10 newer trials. PATIENTS AND METHODS: Analyses are based on individual data from 3,300 patients randomized in 19 trials on an intent-to-treat basis. Two trials had multiple comparisons, leading to a total of 21 pair-wise comparisons. FU doses were similar in both arms in 10 pair-wise comparisons, 15% to 33% higher in the FU-alone arm in six comparisons, and more than 66% higher in five comparisons. RESULTS: Overall analysis showed a two-fold increase in tumor response rates (11% for FU-LV v 21% for FU-LV v 11% for FU [corrected] alone; odds ratio, 0.53; 95% CI, 0.44 to 0.63; P <.0001) and a small but statistically significant overall survival benefit for FU-LV over FU alone (median survival, 11.7 v 10.5 months, respectively; hazards ratio, 0.90; 95% CI, 0.87 to 0.94; P =.004), which were primarily seen in the first year. We observed a significant interaction between treatment benefit and dose of FU, with tumor response and overall survival advantages of FU-LV over FU-alone being restricted to trials in which a similar dose of FU was prescribed in both arms. CONCLUSION: This updated analysis demonstrates, on a large data set, that FU-LV improves both response rate and overall survival compared with FU alone and that this benefit is consistent across various prognostic factors.

Aged↗

Diagnostic performance of panfungal PCR on tissue specimens for the diagnosis of invasive fungal diseases: a systematic review and meta-analysis of the Fungal PCR Initiative (FPCRI).

UNLABELLED: Invasive fungal diseases are difficult to diagnose because of the limited sensitivity of culture. Panfungal PCR amplicon sequencing assays (targeting ribosomal RNA, such as 18S, 28S, ITS) are recommended for fungal identification in histopathology samples showing fungal elements. However, data describing its overall performance and consistency are lacking. This systematic literature review and meta-analysis assessed the performance of panfungal PCR on formalin-fixed paraffin-embedded (FFPE) and non-fixed (fresh or frozen) tissue samples. A systematic literature search was performed to include studies reporting the use of panfungal PCR for fungal identification in FFPE or non-fixed tissue samples. PCR sensitivity and specificity were assessed using the reference standard of histopathology showing fungal elements. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Pooled estimates were obtained using random-effects meta-analysis. Twenty-eight studies were included. In FFPE samples (18 studies, 852 samples), sensitivity and specificity were 75.4% (95% confidence interval [CI], 59.2-86.6) and 93.5% (70.2-98.9), respectively. Sensitivity in non-fixed samples (13 studies, 207 samples) was 86.5% (74.7-93.3), while specificity could not be assessed (insufficient data). Comparative analyses showed a significantly higher sensitivity of panfungal PCR over culture (88.2%; 76-94.7 vs 52.2%; 39-65, P = 0.001). Sub-analyses could not demonstrate the superiority of one PCR target over another due to limited data. Panfungal PCR exhibited adequate sensitivity and good specificity in FFPE samples. Sensitivity was even higher in non-fixed samples and largely superior to culture. Nevertheless, large interstudy variability was observed, warranting interlaboratory studies to define the optimal PCR target and standardized protocols. IMPORTANCE: Invasive fungal diseases are difficult to diagnose because of the low sensitivity of culture. Panfungal PCRs are widely used for fungal identification in tissue specimens but suffer from heterogeneous procedures and performance. This meta-analysis shows an acceptable sensitivity (75.4% and 86.5% in fixed and non-fixed samples, respectively) and good specificity (93.5%) of panfungal PCR, supporting its use, not only on histopathology-positive fixed samples but also in non-fixed samples concomitantly with other diagnostic tools (cultures and fungal-specific PCRs if available). These results provide a strong basis for further standardization of panfungal PCR techniques via interlaboratory assays to assess reproducibility and optimize analytical protocols. CLINICAL TRIALS: This study is registered with PROSPERO as CRD42023461148.

Humans↗

An application of meta-analysis techniques in the evaluation of adverse experiences with antihypertensive agents.

PURPOSE: To investigate the profiles of adverse events (AEs) in randomized controlled trials of antihypertensive agents therapy with the technique of meta-analysis. METHODS: A total of 620 articles were selected from MEDLINE, EMBASE, JAPIC-DOC, JMEDICINE and manual searching. Two independent reviewers examined the 620 selected articles according to the following criteria: (1) the methods of randomization, (2) making for allocating treatments, (3) therapeutic class of drugs, (4) sample sizes, (5) duration of the treatment, (6) primary endpoint, (7) reporting method for all adverse events, (8) method of monitoring AEs, and (9) incidence rates of all reported AEs. To combine the risk difference and risk ratios of incidence between CCBs and beta blockers or diuretics, the method of DerSimonian and Laird based on random effect model was applied. RESULTS: A total of 3073 patients were included in this meta-analysis of serious adverse events (SAEs). There was no significant difference in the total incidence of SAEs between CCBs and diuretics or between CCBs and beta blockers. We found that patients treated with CCBS had 0.14% fewer SAEs compared with the patients treated with diuretics. Contrarily, the patients treated with CCBs had 0.29% more SAEs compared with the patients treated with beta blockers. There was a significant difference between the patients treated with CCBs and those treated with diuretics in the symptoms with headache and oedema. With respect to the comparison between CCBs and beta blockers, flushing occurred 8.75% more frequently in the CCBs group than in the beta blockers group. CONCLUSION: A meta-analysis can be applied to safety analyses of data obtained in clinical trials if all of the RCT articles used include a complete description of adverse experiences.

Journal Article↗

Effectiveness of Caregiver-Mediated Spoken Language Interventions for Children Under Five at Risk of Developmental Language Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Caregiver-mediated interventions are commonly used by Speech and Language Therapists to support early language development. Developmental Language Disorder (DLD) is associated with reduced quality of life throughout the lifespan. Understanding factors that predict intervention success is essential for developing appropriate, cost-effective therapy provision for the approximately 12% of preschool children who present with early markers for Developmental Language Disorder (DLD). This systematic review and meta-analysis examined the effectiveness of caregiver-mediated spoken language interventions for under-fives at risk of DLD, and factors influencing intervention effectiveness. METHODS: A systematic review following PRISMA guidelines was conducted. Five electronic databases were searched to identify experimental studies comparing caregiver-mediated spoken language interventions to control conditions in under-fives presenting with risk factors for DLD. Risk factors included prematurity, socioeconomic factors, caregiver language development concerns, and formal or informal language screening or assessment scores. Twenty-six experimental studies with 1407 child participants were included in qualitative synthesis. Meta-analysis was performed on nine Randomised Controlled Trials involving 947 children. RESULTS: Effectiveness was examined for outcomes including child language gains, child wellbeing, inclusion and attainment. Meta-analysis indicated a significant effect of caregiver-mediated spoken language interventions on language outcomes compared to treatment-as-usual, non-language intervention or waitlist control conditions. Non-language outcomes were evaluated via qualitative synthesis. Interventions significantly improved language development trajectories for under-fives presenting with risk factors or early markers for DLD. CONCLUSION AND IMPLICATIONS: This review contributes to the growing evidence base demonstrating that caregiver-mediated interventions can positively impact language development and wellbeing outcomes for children under five at risk of DLD. These findings support the implementation of caregiver-mediated environmental language interventions in clinical practice to maximise accessibility and cost-effectiveness while delivering optimal outcomes for vulnerable populations. WHAT THIS PAPER ADDS: What is already known on this subject Previous research on caregiver-mediated spoken language interventions has highlighted gaps in the evidence regarding the impact of risk factors, demographic characteristics, dosage and intervention components on child language outcomes. Developmental Language Disorder has relatively high population prevalence, estimated at 7%. Prevalence is associated with risk factors including low household socioeconomic status (SES), prematurity and late language emergence. In contrast to its prevalence, there is low public and professional awareness of DLD and a low diagnostic rate. Therefore, a strengthened evidence base and additional insights into the factors affecting success of family-based interventions is important in order to increase the effectiveness of service provision and care planning for this underserved population. Timely and effective intervention with young children presenting with early markers for DLD has the potential to offer lifelong improvement to their wellbeing, inclusion and attainment outcomes. Recent systematic reviews of the effectiveness of caregiver-mediated language interventions had differences in population age range and diagnostic inclusion criteria. What this paper adds to existing knowledge Our review examines the effectiveness of caregiver-mediated early spoken language interventions on child language, attainment and wellbeing, and on caregiver self-efficacy and adherence to language support strategies. Our population was children under five presenting with risk factors for Developmental Language Disorder, in the absence of other neurodevelopmental or genetic conditions such as intellectual disability or autism. This review adds depth and detail to the evidence base supporting the effectiveness of caregiver-mediated spoken language interventions in improving outcomes for this population of young children, and factors that influence their success. What are the potential or actual clinical implications of this work? The high prevalence of Developmental Language Disorder, estimated at around 7% of the population, and the strong association with risk factors including low SES, prematurity and late language emergence, coupled with the low awareness of DLD and low diagnostic rate, mean that a strengthened evidence base and additional insights into the factors affecting success of family-based interventions can increase the effectiveness of service provision and care planning for this population. Timely and effective intervention in this group of young children has the potential to improve wellbeing and attainment outcomes across the lifespan. This review contributes to our understanding of how to implement cost-effective, socially valid and maximally engaging partnership working with families of young children at risk for DLD.

Humans↗

A systematic review and meta-analysis of treatments for aortic graft infection.

OBJECTIVE: We compared pooled estimates of event rates for amputations, conduit failures, reinfections, early mortalities, and late mortalities in patients with aortic graft infection who were treated by extra-anatomic bypass, rifampicin-bonded prostheses, cryopreserved allografts, or autogenous veins. METHODS: A systematic review was conducted of English language reports in MEDLINE back to 1985 and a meta-analysis was performed on the results. Studies were selected on the basis of medical subject headings aortic, graft, and infection, and also by a standardized and independent quality rating. Inclusion and exclusion criteria were met by 37 clinical studies. Pooled estimates of mean event rates for amputations, conduit failures, reinfections, early (< or =30 day) mortalities, and late (>30 days) mortalities were determined for each treatment modality. Tests of heterogeneity and sensitivity analyses were performed. RESULTS: Fixed effect analyses, derived after tests of heterogeneity, yielded overall pooled estimates of mean event rates for all outcomes combined of 0.16 for extra-anatomic bypass, 0.07 for rifampicin-bonded prostheses, 0.09 for cryopreserved allografts, and 0.10 for autogenous vein; a lower value signifies fewer overall events associated with the treatment modality. Overall, the robustness of our meta-analysis was demonstrated by the reasonable heterogeneity of pooled data from individual studies (Q statistic <25; P >.1 for all treatment outcomes across all modalities) and the limited variability of outcomes after sensitivity analyses. CONCLUSION: Although limited by the design of individual published studies whose data were pooled together in this meta-analysis, our results lead to questions concerning whether extra-anatomic bypass should remain the gold standard for treatment of aortic graft infection.

Antibiotics, Antitubercular↗

Family psychiatric history evidence on the nosological relations of DSM-IV ADHD combined and inattentive subtypes: new data and meta-analysis.

BACKGROUND: A key issue in the nosology of attention deficit hyperactivity disorder (ADHD) has concerned whether the DSM-IV combined (ADHD-C) and primarily inattentive (ADHD-PI) subtypes are in fact distinct disorders, or instead are fairly closely related, perhaps differing only in severity. Pertinent to this question, but in short supply, are data on family psychiatric history. METHOD: We present new data followed by a meta-analysis. For the new data 210 children were well-characterized via structured interview and multi-informant ratings as ADHD-C or ADHD-PI. Three hundred and thirty-five parents completed structured diagnostic interviews to determine whether they had ADHD-C or ADHD-PI. Comorbid disorders were also assessed. For the meta-analysis, 6 existing family-history data sets using DSM-IV subtypes were pooled and analyzed (total N = 4120). RESULTS: The new family study found support for subtype-specific transmission, but the effect was small. Girls with ADHD-C had more severe family psychiatric histories (non-ADHD disorders in parents) than girls with ADHD-I, but this subtype effect did not occur for boys. The meta-analysis of 6 data sets implemented a model-fitting methodology. Despite inconsistent results across individual studies, the pooled data consistently suggested that (1) some degree of subtype specific transmission is occurring, (2) the effect is small, (3) non-specific (gradient) transmission also occurs, specifically in families of children with ADHD-C. CONCLUSION: The much-debated relation between these two most prevalent ADHD subtypes is best modeled via two processes transmitting in families. One process is distinct for the two syndromes, and the other is shared. We briefly suggest neuropsychological models that would account for this state of affairs and suggest future research to refine the nosology with these findings in mind.

Adult↗

Association between fruit and vegetable consumption and oral cancer: a meta-analysis of observational studies.

BACKGROUND: Oral cancer ranks as the seventh most common form of cancer worldwide. Recent reports have examined the effect of fruit and vegetable intake on the risk of oral cancer, but results are controversial. OBJECTIVE: A meta-analysis was performed to arrive at quantitative conclusions about the contribution of fruit and vegetable intakes to the occurrence of oral cancer. DESIGN: A comprehensive, systematic bibliographic search of medical literature published up to September 2005 was conducted to identify relevant studies. Separate meta-analyses were conducted for fruit and vegetable consumption. The effect of portion or daily intake of fruit or vegetables on the risk of oral cancer was calculated. A multivariate meta-regression analysis was performed to explore heterogeneity. This multivariate meta-regression analysis examined the effect of quality score, the type of cancers included, citrus fruit and green vegetable consumption, and the time interval for dietary recall of the studies on the role of fruit or vegetable consumption in the risk of oral cancer. The presence of publication bias was assessed with a funnel plot for asymmetry. RESULTS: Sixteen studies (15 case-control studies and 1 cohort study) met the inclusion criteria and were included in the meta-analysis. The combined adjusted odds ratio (OR) estimates showed that each portion of fruit consumed per day significantly reduced the risk of oral cancer by 49% (OR: 0.51; 95% CI: 0.40, 0.65). For vegetable consumption, the meta-analysis showed a significant reduction in the overall risk of oral cancer of 50% (OR: 0.50; 95% CI: 0.38, 0.65). The multivariate meta-regression showed that the lower risk of oral cancer associated with fruit consumption was significantly influenced by the type of fruit consumed and by the time interval of dietary recall. CONCLUSION: The consumption of fruit and vegetables is associated with a reduced risk of oral cancer.

Adolescent↗

Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long term remission after medical therapy of Graves' disease.

Patients with the hyperthyroidism of Graves' disease (GDH) have a higher risk of relapse after antithyroid drug therapy (ATD) therapy when TSH receptor antibodies (TRAb) are positive, but the practical clinical implication of TRAb as a predictor for relapse is still much debated. This study was undertaken to investigate by meta-analysis the results from the literature on the use of TRAb as predictor of long term (i.e. at least 1 yr) relapse after ATD. Eighteen publications from 1975-1991 fulfilled the criteria of 1) availability of TRAb at the end of ATD treatment, 2) at least 1 yr of follow-up after ATD, 3) data presentation in a form suitable for meta-analysis, and 4) no other thyroid-related therapy during the follow-up period. The 10 prospective studies, 5 of which measured TSH binding inhibiting immunoglobulins (total n = 597) and 5 of which measured thyroid-stimulating antibodies (n = 340), were computed together because no significant differences were found. In contrast, retrospective and prospective studies differed. In the prospective studies, the odds reduction of relapse showed 65% less risk of relapse when TRAb were absent compared to that in TRAb-positive patients (P < 0.00001). The present meta-analysis has, thus, confirmed in a large number of patients (n = 1524) that absence of TRAb is significantly protective against relapse of GDH after ATD treatment. However, 25% of the patients are "misclassified," and the main questions arising from the study are, therefore, the following. 1) Is it worthwhile to use TRAb as predictor of relapse? 2) Should patients with GDH continue ATD until TRAb becomes negative, rather than for a fixed period? The available methods for TRAb do not allow sufficiently high prediction of relapse or remission after ATD for the individual patient.

Antibodies↗

Does psi exist? Comments on Milton and Wiseman's (1999) meta-analysis of ganzfeld research.

J. Milton and R. Wiseman (1999) attempted to replicate D. Bem and C. Honorton's (1994) meta-analysis, which yielded evidence that the ganzfeld is a suitable method for demonstrating anomalous communication. Using a database of 30 ganzfeld and autoganzfeld studies, Milton and Wiseman's meta-analysis yielded an effect size (ES) of only 0.013 (Stouffer Z = 0.70, p = .24, one-tailed). Thus they failed to replicate Bem and Honorton's finding (ES = 0.162, Stouffer Z = 2.52, p = 5.90 x 10(-3), one-tailed). The authors conducted stepwise performance comparisons between all available databases of ganzfeld research, which were argued not to be lacking in quality. Larger aggregates of such studies were formed, including a database comprising 79 ganzfeld-autoganzfeld studies (ES = 0.138, Stouffer Z = 5.66, p = 7.78 x 10(-9)). Thus Bem and Honorton's positive conclusion was confirmed. More accurate population parameters for the ganzfeld and autoganzfeld domains were calculated. Significant bidirectional psi effects were also found in all databases. The ganzfeld appears to be a replicable technique for producing psi effects in the laboratory.

Humans↗