Describing and interpreting the methodological and statistical techniques in meta-analyses

Pojam meta-analize udomaćio se kao termin koji označava tumačenje rezultata iz znanstvene literature i stvaranje konačnog zaključka o prihvatljivosti rezultata istraživanja kojima se ispituju slične intervencije, tehnike ili liječenja. Meta-analiza je postala neophodna u razumijevanju velike zbirke neobrađenih podataka ili literature koja je ponekad proturječna, nedosljedna i nejasna o nekoj temi te u razumijevanju prave važnosti statističkih rezultata kod obrade neke znanstvene teme kao što je, primjerice, učinkovitost. Ne treba samo razumjeti motivaciju za meta-analizu, već i tehnike kojima sumiramo rezultate različitih istraživanja i koje pružaju odgovarajuće statističko promatranje i tumačenje rezultata. Poseban izazov predstavljaju različiti ustroji istraživanja, različiti kriteriji prihvaćanja za uključenje u neko istraživanje, posebno u medicinsko-kliničko ispitivanje, te mogući različiti pristupi tumačenju rezultata, iako ovo zadnje nije prevladavajuće. Općenito govoreći, istraživanja koja obuhvaćaju ispitivanje uloge neke intervencije kao što je, primjerice, sniženje koncentracije kolesterola i njen utjecaj na kardiovaskularno zdravlje, obrađuju sličnu temu te ako se rezultati tih istraživanja ne podudaraju, uloga meta-analize je usporediti sve rezultate i donijeti krajnji zaključak o pozitivnom, negativnom ili nejasnom utjecaju smanjene koncentracije lipida na kardiovaskularno zdravlje. Prikaz pristupa meta-analizi je jako vrijedan budući da u većini slučajeva nudi objašnjenje statističkih pristupa, njihovog značenja, svrhe i krajnjeg utjecaja na tumačenje meta-analize. Stoga bi istraživač, kad ima na raspolaganju elemente meta-analize, trebao razumjeti prednosti i ograničenja tog načina tumačenja rezultata iz literature.The term, meta-analysis, has become a regular description for interpreting results from the scientific literature and hopefully reaching a definitive conclusion concerning the reasonableness of results of studies investigating similar interventions, techniques or treatments. It has become a necessity for understanding the sometimes huge repository of conflicting, inconsistent or inconclusive literature or raw data on a subject and understanding the true relevancy of the statistical results in addressing a scientific question such as efficacy. One has to understand, not only the motivation for a meta-analysis, but the techniques employed to help synthesize results from different studies giving them appropriate statistical scrutiny and interpreting the conclusions. A particular challenge is the differing designs of studies, differing eligibility criteria for entry into the study, especially in the medical clinical trial and possibly non similar approaches in interpreting the results, although this latter point is not too prevalent. For the most part studies investigating the role of a particular intervention such as lowering cholesterol and the impact on cardiovascular health address a similar question and should studies not all agree on the results, the role of meta-analysis is to hopefully put all the results together and reach a definitive conclusion about the positive, negative or inconclusive impact on lowering lipid levels and cardiovascular health. One should appreciate an overview of the approach to meta-analysis assuring mostly the understanding of the statistical approaches, their meaning, purpose and ultimate impact on the interpretation of the meta-analysis. Thus having been exposed to the elements of the meta-analysis one should understand the advantages and limitations of this approach to interpreting results from the literature

Random Regression Models Based On The Elliptically Contoured Distribution Assumptions With Applications To Longitudinal Data

We generalize Lyles et al.’s (2000) random regression models for longitudinal data, accounting for both undetectable values and informative drop-outs in the distribution assumptions. Our models are constructed on the generalized multivariate theory which is based on the Elliptically Contoured Distribution (ECD). The estimation of the fixed parameters in the random regression models are invariant under the normal or the ECD assumptions. For the Human Immunodeficiency Virus Epidemiology Research Study data, ECD models fit the data better than classical normal models according to the Akaike (1974) Information Criterion. We also note that both univariate distributions of the random intercept and random slope and their joint distribution are non-normal short-tailed ECDs, and that the error term is distributed as a non-normal long-tailed ECD if we don’t use the low undetectable limit or half of it to replace the undetectable values. Instead, we use the ECD cumulative distribution function to calculate the contribution to the likelihood due to the undetectable values

Short-term effect of fenofibrate on C-reactive protein: A meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>C-reactive protein (CRP) is positively associated with risk for cardiovascular disease and all-cause mortality. Some but not all randomized and non-randomized clinical trials found significant associations between fenofibrate therapy and CRP but the direction and magnitude of the association varied across studies. The duration of treatment, patient populations and sample sizes varied greatly, and most short-term studies (i.e., ≤ 12 weeks) had fewer than 50 patients. In this study we meta-analyzed randomized clinical trials to determine the short-term effect of fenofibrate on CRP.</p> <p>Methods</p> <p>Two reviewers independently searched PubMed and other online databases for short-term randomized clinical trials that reported CRP concentrations before and after fenofibrate treatment. Of the 81 studies examined, 14 studies with 540 patients were found eligible. Data for the change in CRP and corresponding measures of dispersion were extracted for use in the meta-analysis.</p> <p>Results</p> <p>The weighted mean CRP concentrations before and after fenofibrate therapy were 2.15 mg/L and 1.53 mg/L (-28.8% change), respectively. Inverse-variance weighted random effects meta-analysis revealed that short-term fenofibrate treatment significantly lowers CRP by 0.58 mg/L (95% CI: 0.36-0.80). There was significant heterogeneity between studies (Q statistic = 64.5, <it>P</it>< 0.0001, I²= 79.8%). There was no evidence of publication bias and sensitivity analysis revealed that omitting any of the 14 studies did not lead to a different conclusion from the overall meta-analysis result.</p> <p>Conclusion</p> <p>Short-term treatment with fenofibrate significantly lowers CRP concentration. Randomized trials that will recruit patients based with high baseline CRP concentrations and with change in CRP as a primary outcome are needed.</p

Emergent Endotracheal Intubation and Mortality in Traumatic Brain Injury

Objective: To determine the relationship between emergent intubation (emergency department and field intubation cases combined) and mortality in patients with traumatic brain injury (TBI) while controlling for injury severity.Methods: Retrospective observational study of 981 (35.2% intubated, 64.8% not intubated) patients with TBI evaluating the association between intubation status and mortality. Logistic regression was used to analyze the data. Injury severity measures included Head/Neck Abbreviated Injury Scale (H-AIS), systolic blood pressure, type of head injury (blunt vs. penetrating), and a propensity score combining the effects of several other potential confounding variables. Age was also included in the model.Results: The simple association of emergent endotracheal intubation with death had an odds ratio (OR) of 14.3 (95% CI = 9.4 – 21.9). The logistic regression model including relevant covariates and a propensity score that adjusted for injury severity and age yielded an OR of 5.9 (95% CI = 3.2 – 10.9).Conclusions: This study indicates that emergent intubation is associated with increased risk of death after controlling for a number of injury severity indicators. We discuss the need for optimal paramedic training, and an understanding of the factors that guide patient selection and the decision to intubate in the field. [WestJEM.2008;9:184-189

Intercostal muscle flap reduces the pain of thoracotomy: A prospective randomized trial

BackgroundThoracotomy is associated with significant pain and morbidity.MethodsWe performed a prospective randomized trial over 4 months. Patients were randomized to a standard posterior-lateral thoracotomy or an identical procedure, except an intercostal muscle was harvested from the lower rib (to protect the intercostal nerve) before chest retraction. To ensure an equal distribution among both groups, patients were stratified by race, sex, and type of pulmonary resection. All patients received similar pain management. Pain was assessed by using multiple pain scores during hospitalization and after discharge. Outcomes assessed were pain scores, spirometric values, analgesic use, and activity level.ResultsThere were 114 patients. The median time for intercostal muscle harvesting was 3.7 minutes. The numeric pain scores were lower for the intercostal muscle group on postoperative days 1 and 2 and at weeks 1, 2, 3, 4, 8, and 12 (P < .05 for all). In addition, patients in the intercostal muscle group had a smaller decrease in spirometric values, were less likely to be using analgesics, and were more likely to have returned to normal activity.ConclusionsThe harvesting of an intercostal muscle flap before chest retraction decreases the pain of thoracotomy and leads to a lower decrease in spirometry. In addition, patients have less pain at 1, 2, 3, 4, 8, and 12 weeks postoperatively and are less likely to be using narcotics. Finally, it offers a pedicled muscle flap that takes little time to harvest and is able to buttress all bronchi after lobectomy

Regional Disparities in Ovarian Cancer in the United States

The aim of this study was to investigate the association between geographic regions and ovarian cancer disparities in the United States.Data from the Surveillance, Epidemiology, and End Results (SEER) Program was used to identify women diagnosed with ovarian cancer. 18 registries were divided into two groups: South region and US14 region. Chi-Square tests were used to compare proportions, the logistic regression model to evaluate the association between 5-year survival and other variables, and the Cox proportional hazards model to estimate hazard ratios.The South region had a lower incidence rate than the US14 region (12.0 vs. 13.4 per 100,000), and a lower 5-year observed survival rate (37.5% vs. 39.8%). White women living in the US14 region had the best overall survival, compared to white women living in the South region, and black women living in both regions. Women in the South region were less likely to have insurance (6.6% vs. 2.7%, p&lt;0.0001) and surgery (73.4% vs. 76.2%, p&lt;0.0001). Women living in the South were 1.4 times more likely to die after five years of diagnosis than women living in the US14 region. The data confirmed regional disparities in ovarian cancer in the United States, showing women living in the South region were disadvantaged in ovarian cancer survival regardless of race, black or white. Future research focusing on the identification of contributing factors to regional disparity in ovarian cancer is necessary to develop practical approaches to improve health outcomes related to this lethal disease

Southeastern cancer study group: Breast cancer studies 1972–1982

During the past 10 years, the Southeastern Cancer Study Group (SECSG) has been engaged in one major adjuvant study and three major advanced disease studies for patients with adenocarcinoma of the breast. The adjuvant study is demonstrating that six months of adjuvant CMF is the therapeutic equivalent of 12 months and that post-operative irradiation is of no added therapeutic benefit. In patients with advanced disease, a low dose 5 drug combination of CMFVP induces more objective responses than single agent 5FU, but improves survival only for those patients with liver metastases when compared to the sequential use of the same 5 single agents. The three drug combination, CAF, utilizing doxorubicin, induces more objective responses than low dose CMFVP, but it does not improve overall survival. The subsets of patients with bone-only metastases, with local chest wall recurrence and with nodular lung metastases benefit from CAF in terms of a longer duration of disease control and longer duration of unmaintained remission, but have only a marginal improvement in survival. The addition of a phase active combination, CAMELEON, (i.e., sequentially alternating therapy) to CAF has not improved the duration of disease control and survival for patients with liver metastases, lymphangitic and nodular lung metastases compared to CAF. Aggressive combination chemotherapeutic approaches to patients with advanced disease provide better and longer disease and tumor control but only marginal improvements in overall survival. Adding additional agents to a maximally tolerable regimen has not improved the therapeutic outcome