Quantitative synthesis in systematic reviews

The final common pathway for most systematic reviews is a statistical summary of the data, or meta-analysis. The complex methods used in meta-analyses should always be complemented by clinical acumen and common sense in designing the protocol of a systematic review, deciding which data can be combined, and determining whether data should be combined. Both continuous and binary data can be pooled. Most meta-analyses summarize data from randomized trials, but other applications, such as the evaluation of diagnostic test performance and observational studies, have also been developed. The statistical methods of meta-analysis aim at evaluating the diversity (heterogeneity) among the results of different studies, exploring and explaining observed heterogeneity, and estimating a common pooled effect with increased precision. Fixed-effects models assume that an intervention has a single true effect, whereas random-effects models assume that an effect may vary across studies. Meta-regression analyses, by using each study rather than each patient as a unit of observation, can help to evaluate the effect of individual variables on the magnitude of an observed effect and thus may sometimes explain why study results differ. It is also important to assess the robustness of conclusions through sensitivity analyses and a formal evaluation of potential sources of bias, including publication bias and the effect of the quality of the studies on the observed effect.     

A guide to interpreting discordant systematic reviews

Systematic reviews are becoming prominent tools to guide health care decisions. As the number of published systematic reviews increases, it is common to find more than 1 systematic review addressing the same or a very similar therapeutic question. Despite the promise for systematic reviews to resolve conflicting results of primary studies, conflicts among reviews are now emerging. Such conflicts produce difficulties for decision-makers (including clinicians, policy-makers, researchers and patients) who rely on these reviews to help them make choices among alternative interventions when experts and the results of trials disagree. The authors provide an adjunct decision tool--a decision algorithm--to help decision-makers select from among discordant reviews.     

Formulating questions and locating primary studies for inclusion in systematic reviews

Much time and effort are spent on designing primary research studies. Similar care must be given to planning systematic reviews. The review should be based on an important, well-focused question that is relevant to patient care. By formulating the question properly, the criteria that primary studies must meet to be included in the review become clear. These criteria, which comprise the types of persons involved, exposure, control group, outcomes, and study designs of interest, can then be refined so that they are clinically relevant, sensible, and workable. Inclusion criteria that are too narrow will limit the amount of data in the review, thereby increasing the risk for chance results and making the review less useful for the reader. Reviews should include studies whose designs offer the least biased answer to the question being asked. To maximize available data and reduce the risk for bias, as many relevant studies as possible need to be identified, regardless of publication status or language. Multiple overlapping search strategies should therefore be used and must be carefully planned. Strategies include searching the many electronic databases available (after careful consideration of which terms to enter), manually searching journals and conference proceedings, searching bibliographies of articles, searching existing registers of studies, and contacting companies or researchers. The time taken to formulate the question adequately and develop appropriate searches will increase the chance of producing a high-quality, meaningful review.     

How consumers and policymakers can use systematic reviews for decision making

OBJECTIVE: To compare the effects of aspartame-sweetened and sucrose-sweetened soft drinks on food intake and appetite ratings of female restrained eaters. SUBJECTS: Fourteen female students, shown to have eating restraint. METHODS: Subjects were given four drinks (330 ml) of aspartame-sweetened lemonade, sucrose-sweetened lemonade and carbonated mineral water on three separate days. Seven of the subjects were informed of the drink type they were consuming on each occasion. MEASUREMENTS: Appetite ratings were recorded and energy and macronutrient intakes were measured during the study day and day after leaving the department. RESULTS: During the first study day energy intake was lower whilst drinking the sucrose-sweetened lemonade compared with the aspartame-sweetened lemonade, although neither differed significantly from energy intakes during the day the drank water. When the calories from the sucrose-sweetened lemonade were included (1381 kJ, 330 Kcal) energy intake did not differ between treatments. The following day energy intake was significantly higher after the aspartame-sweetened lemonade compared with both sucrose-sweetened lemonade and the water due to an increase in the amount of carbohydrate consumed and resulted in a higher total energy intake over the two days studied. Knowledge of the drink types had no effect on energy intake or macronutrient intake. Appetite ratings did not differ between drinks and were not affected by knowledge of the drink types. CONCLUSION: These results suggest that in females with eating restraint, substituting sucrose-sweetened drinks for diet drinks does not reduce total energy intake and may even result in a higher intake during the subsequent day.     

Applying the results of trials and systematic reviews to individual patients

Your patient is a 60-year-old hypertensive, alcoholic woman whose symptomless atrial fibrillation was first documented 3 months ago. An echocardiogram shows an enlarged left atrium, rendering successful cardioversion unlikely. She tells you that both of her parents had severe strokes that made the last years of their lives horrible, and she is terrified of having a stroke. You know that a meta-analysis of 5 randomized trials of warfarin in nonvalvular atrial fibrillation demonstrated a 68% relative risk reduction (RRR) in stroke (1). You consider prescribing warfarin for this patient but know that she would not have qualified for the study because alcoholism increases her risk for major hemorrhage (2).     

Rationale for retention following orthodontic treatment

One pyranocoumarin (xanthyletin, 1) and two acridone alkaloids (2',2'-dimethyl-(pyrano5',6':3:4)-1,5-dihydroxy, 6-methoxy, 10-methylacridone, 3, and citpressine-I, 4), were isolated from the roots of Citrus deliciosa Ten (Rutacea). Their structures were elucidated by spectroscopic methods. Reported 13C NMR assignments of alkaloid 3 have been corrected and those of alkaloid 4 are reported for the first time Alkaloid 3 was found to have antispasmodic effect on isolated ileum segments excised from male rabbits.     

Meta-analyses and systematic reviews of psychological treatments for chronic pain: Relevance to an evidence-based practice.

As evidence-based practitioners become more reliant on systematic reviews to inform treatment, it becomes important to systematize reporting details as well as improve the quality of the primary studies that will later be incorporated into this secondary literature. In this article, the authors consider several specific factors that can serve this function in the area of chronic pain: (a) adhering to a standardized set of reporting standards; (b) measuring a standardized set of short- and long-term outcome variables; (c) providing information about individual differences; and (d) providing detailed, easily accessible documentation of the treatment program (or progams). The article also highlights ways that practitioners and researchers can collaborate on treatment outcome research, thereby improving the ability to discover and disseminate effective treatments for patients who suffer from chronic pain. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rationale for banning abortions late in pregnancy

Chronic myelogenous leukemia (CML) is a myelo-proliferative disorder which, after a chronic phase which lasts an average of 3 years, evolves into an acute disease which is resistant to chemotherapy. Nevertheless, a few studies have reported cases in which partial or complete hematologic, cytogenetic and/or molecular remission of the disease were observed either spontaneously or after non intensive chemotherapy, with or without medullar aplasia. Some of these patients later relapsed into a blast crisis. We report a case of CML with clinical and hematologic remission for 19 years after two cycles of busulphan not causing medullar aplasia, negative for the BCR/ABL gene by Southern blot but with the gene's mRNA detectable by hot start nested RT-PCR.     

Rationale for total nephrectomy for suspected renal cell carcinoma

Effects of hyperthermia and cell densities on inhibitory activity of ascorbic acid on DNA synthesis in Ehrlich ascites tumor cells were studied. When cells at a low density of 5 x 10(3)/ml were treated with 75 microM ascorbic acid for 1 h, DNA synthesis was inhibited after treatment at 37 degrees C and the inhibition was significantly enhanced at 42 degrees C. At a cell density as high as 1 x 10(5)/ml, however, inhibition did not occur at 37 degrees C or 42 degrees C. In contrast, dehydroascorbic acid was inactive even at a low cell density under similar conditions. Inhibitory effects of ascorbic acid on DNA synthesis were also markedly enhanced by treatment at 40 degrees C. DNA synthesis was not inhibited in the absence of the drug. Furthermore, mice transplanted with cells treated with a combination of 75 microM ascorbic acid and hyperthermia at 42 degrees C, considerably prolonged their survival time in comparison with untreated cells. Addition of ascorbic acid to hyperthermia is suggested to be an advantageous treatment for cancer.     

Randomised trial of educational visits to enhance use of systematic reviews in 25 obstetric units

OBJECTIVE: To evaluate the effectiveness of an educational visit to help obstetricians and midwives select and use evidence from a Cochrane database containing 600 systematic reviews. DESIGN: Randomised single blind controlled trial with obstetric units allocated to an educational visit or control group. SETTING: 25 of the 26 district general obstetric units in two former NHS regions. SUBJECTS: The senior obstetrician and midwife from each intervention unit participated in educational visits. Clinical practices of all staff were assessed in 4508 pregnancies. INTERVENTION: Single informal educational visit by a respected obstetrician including discussion of evidence based obstetrics, guidance on implementation, and donation of Cochrane database and other materials. MAIN OUTCOME MEASURES: Rates of perineal suturing with polyglycolic acid, ventouse delivery, prophylactic antibiotics in caesarean section, and steroids in preterm delivery, before and 9 months after visits, and concordance of guidelines with review evidence for same marker practices before and after visits. RESULTS: Rates varied greatly, but the overall baseline mean of 43% (986/2312) increased to 54% (1189/2196) 9 months later. Rates of ventouse delivery increased significantly in intervention units but not in control units; there was no difference between the two types of units in uptake of other practices. Pooling rates from all 25 units, use of antibiotics in caesarean section and use of polyglycolic acid sutures increased significantly over the period, but use of steroids in preterm delivery was unchanged. Labour ward guidelines seldom agreed with evidence at baseline; this hardly improved after visits. Educational visits cost pound860 each (at 1995 prices). CONCLUSIONS: There was considerable uptake of evidence into practice in both control and intervention units between 1994 and 1995. Our educational visits added little to this, despite the informal setting, targeting of senior staff from two disciplines, and donation of educational materials. Further work is needed to define cost effective methods to enhance the uptake of evidence from systematic reviews and to clarify leadership and roles of senior obstetric staff in implementing the evidence.     

Rationale for using invasive thermometry for regional hyperthermia of pelvic tumors

PURPOSE: Invasive thermometry for regional hyperthermia is time-consuming, uncomfortable, and risky for the patient. We tried to estimate the benefit/cost ratio of invasive thermometry in regional hyperthermia using the radiofrequency system BSD-2000. METHODS AND MATERIALS: We evaluated 182 patients with locally advanced pelvic tumors that underwent regional hyperthermia. In every patient a tumor-related temperature measurement point was obtained either by invasive or minimally invasive catheter measurement tracks. In the earlier period for every patient an intratumoral measurement point was decided as obligatory and intratumoral catheters were implanted intraoperatively, CT guided, or under fluoroscopy. In the later period, invasive thermometry often was avoided, if a measurement point in or near the tumor was reached by an endoluminally inserted catheter (rectal, vaginal, cervical, urethral, or vesical). For every patient side effects and complications referred to thermometry were evaluated and compared with the potential benefit of the invasively achieved temperature data. The suitability of endolumimally registered temperatures is analyzed to estimate local feasibility (specific absorption rate achieved) and local effectiveness (thermal parameters correlated with response). RESULTS: In 74 of 182 patients invasive thermometry was performed, at most CT-guided for soft tissue sarcomas and rectal recurrences. In 14 of 74 (19%) side effects such as local inflammation, pain, or abscess formation occurred that enforced removal of the catheter. However, local problems were strongly correlated with the dwell time of the catheter and nearly never occurred for dwell times less than 5 days. Fortunately, no fatal complications (e.g., bleeding or perforation) occurred during or after implantation which could be attributed to the invasive thermometry procedure. Endoluminal tumor-related temperature rises per time unit (to estimate power density) were correlated with intratumoral rises at the same patients (where both measurements were available). For a subgroup of patients pooled in two Phase II studies with rectal (n = 37) and cervical (n = 18) carcinomas thermal parameters derived from endoluminal measurements were correlated with response or local control, resp. CONCLUSIONS: If a tumor-related endoluminal temperature measurement point is available, additional invasive thermometry gives no further information to improve the power deposition pattern. For primary rectal and cervical cancer, and probably as well for prostate, bladder and anal cancer, endoluminal measurements are suitable to estimate local feasibility and effectiveness. Therefore, invasive thermometry is dispensable in the majority of patients. In some selected cases, temperature measurement in the tumor center is required to estimate the maximum temperature. In those cases, dwell time of catheters should be minimized--and it should be considered to perform invasive thermometry at the beginning (one or two heat treatments).     

New paradigms for anterior tooth preparation. Rationale and technique

A biologic and esthetic rationale has been presented along with a simplified controlled technique to achieve predictable results (Figures 13A and 13B). The clinician is constantly faced with the challenge of developing room for esthetic material while preserving the biologic objectives. Using the three essential anterior tooth preparation keys (incisal edge, reduction requirements, and the biologic zone) enhances predictability. Developing the incisal edge relative to the dynamics of facial esthetics provides the initial starting point of tooth preparation. The reduction requirements are designed to satisfy the mechanical principles, address the pulpal concerns, and preserve the structural requirements of the tooth. The biologic zone can be developed by using the total dentogingival complex measurements and will clinically aid in the determination of cervical limitations to providing intracrevicular margin location.     

Framework for Measuring the Rationale Clarity of AEC Design Decisions

Current architecture, engineering, and construction (AEC) design processes often rely on precedent to resolve complex decisions. However, changes to stakeholder concerns, design methods, and building products devalue much of this precedent knowledge. Project teams need to clearly communicate their decision rationale to develop consensus about design decisions. This study reviews a broad range of relevant theory from decision-based design, decision analysis, decision theory, linguistics, logic, organization theory, and social welfare. Rationale is defined as a set of assertions regarding distinct components (i.e., managers, stakeholders, designers, gatekeepers, goals, constraints, alternatives, and analysis) that support design decisions. Conditions of clarity (i.e., coherent, concrete, connected, consistent, credible, certain, and correct) are also defined. These definitions are used to measure the clarity of assertions, components, and the rationale as a whole. Taken together, this rationale clarity framework (RCF) provides a structured view that enables an objective evaluation of design decision methods.     

Skills training for bicultural competence: Rationale and application.

Describes the advantages of the social skills training (SST) model and the utility of the concept of bicultural competence as more adequately meeting mental health needs of Native Americans than present government practices. An illustration of the process of culturally adapting SST is provided by outlining an assertion training program developed with and for Native Americans. The specifics were refined over 1 yr as a result of interactions with 30 tribal groups and agencies. Situations were identified in which Native Americans wished they had behaved differently (e.g., challenging employers who stereotyped Native Americans). The Native American traditions of role modeling, apprenticeship training, and group consensus parallel the SST principles of instruction, modeling, behavior rehearsal, reinforcement, feedback, skill improvement, and generalization to the natural environment. The key instructional element of this assertion program stressed the situation-specific nature of assertiveness. Discrimination skills in bicultural rights, language styles, social expectations, and social reinforcers were essential in training for bicultural competence. Native American group support and consensus were noticeable during behavior rehearsal and reinforcement segments. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)