Laparoscopic vs conventional appendectomy--a meta-analysis of randomised controlled trials

A comparison was made of the dynamics of sympathoadrenal activity in 11 age-matched male and female rats, under basal conditions and after exposure to footshock. Rats were prepared with indwelling catheters in the tail artery 24 h before the experiment. Measurements were made of plasma corticosterone (COR), norepinephrine (NE), epinephrine (EPI), dihydroxyphenylalanine (DOPA), dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC) under resting conditions, after transfer to the shock box (novelty) and at various times after footshock. Under basal conditions, males have significantly higher blood pressure and plasma DHPG/NE ratios but lower plasma levels of COR, NE and DOPAC than females. Three min after exposure to the shock chamber (novelty stress) there were significant increases in COR, EPI, NE and DHPG in both sexes, while DOPA increased only in females and DOPAC remained unchanged in both sexes. Footshock produced a further increase in EPI, NE and DOPAC within 2 min, which lasted about 15 min. There were significant sex differences in the extent and duration of the response of COR, EPI and DHPG. The data show that the female sympathoadrenal system is more reactive than that of the male to the stresses of a novel environment and footshock. The smaller DHPG/NE ratios in females at rest and after stress suggest that neuronal uptake of NE is lower in females than in males. The finding that stress produces larger increments of plasma DOPA and DOPAC in female rats indicates that tyrosine hydroxylase in the sympathetic nerve terminals and adrenal medulla may also be higher than in males.     

The Internet and randomised controlled trials

Several factors constrain the implementation of Randomised Controlled Trials (RCTs). To obtain large sample sizes a multicentred multinational trial may be necessary or a long sampling period. The larger the trial the larger is the unit cost. To allow larger sample sizes, shorter sampling periods and lower unit costs, new methods are needed. The Internet and in particular the WWW provides such an opportunity. The WWW can provide global access, fast interaction and automation. A prototype Internet Trials Service (ITS) is currently being tested with a real international clinical trial (the Growth Restriction Intervention Trial--GRIT). The ITS is hosted on a Web server. It provides a series of HTML documents that describe the GRIT protocol. Registered centres may enter patients into the GRIT trial via ITS. Java applets are used to collect trial data before returning the study number and randomisation. ITS assumes all trial data will be intercepted by a sniffer. Therefore no information is sent that could specifically identify a patient, this must be sent later by more secure means. ITS assumes that trial centres can be spoofed. To authenticate the patients entered into the trial and the trial data sent, a regular audit report is sent to each centre by secure means for confirmation. By using Java, a full functional data entry system can be developed that runs locally within any Java enabled browser. It can perform data validation locally and also provide a sophisticated user interface.     

Language bias in randomised controlled trials published in English and German

BACKGROUND: Some randomised controlled trials (RCTs) done in German-speaking Europe are published in international English-language journals and others in national German-language journals. We assessed whether authors are more likely to report trials with statistically significant results in English than in German. METHODS: We studied pairs of RCT reports, matched for first author and time of publication, with one report published in German and the other in English. Pairs were identified from reports round in a manual search of five leading German-language journals and from reports published by the same authors in English found on Medline. Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors' identities, affiliations, and other characteristics of trial reports. Main study endpoints were selected by two investigators who were unaware of trial results. Our main outcome was the number of pairs of studies in which the levels of significance (shown by p values) were discordant. FINDINGS: 62 eligible pairs of reports were identified but 19 (31%) were excluded because they were duplicate publications. A further three pairs (5%) were excluded because no p values were given. The remaining 40 pairs were analysed. Design characteristics and quality features were similar for reports in both languages. Only 35% of German-language articles, compared with 62% of English-language articles, reported significant (p < 0.05) differences in the main endpoint between study and control groups (p = 0.002 by McNemar's test). Logistic regression showed that the only characteristic that predicted publication in an English-language journal was a significant result. The odds ratio for publication of trials with significant results in English was 3.75 (95% CI 1.25-11.3). INTERPRETATION: Authors were more likely to publish RCTs in an English-language journal if the results were statistically significant. English language bias may, therefore, be introduced in reviews and meta-analyses if they include only trials reported in English. The effort of the Cochrane Collaboration to identify as many controlled trials as possible, through the manual search of many medical journals published in different languages will help to reduce such bias.     

Overcoming contextual limitations on problem-solving transfer.

Five experiments investigated transfer from multiple analogs to a superficially dissimilar target problem. When subjects explicitly compared the analogs and then immediately attempted to solve the target problem in the context of a single experiment, transfer was obtained with significant frequency even without a hint that the analogs and target were related. Prehint transfer was sharply reduced or eliminated when the source analogs and the target were presented in different contexts, even when the transfer test was immediate. However, prehint transfer was enhanced, even after a context shift and a week-long delay between reading the source analogs and solving the problem, when the following conditions were met: The target problem was reworded slightly to emphasize a structural feature that it shared with the analogs; three rather than two source analogs were provided; and detailed, schema-oriented questions were used to help subjects focus on the problem-relevant aspects of the stories. Although spontaneous transfer between small numbers of dissimilar analogs is difficult to obtain, it can be achieved by manipulations that foster abstraction of a problem schema from the training examples. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials

OBJECTIVE: To evaluate the efficacy of pentoxifylline therapy in improving the walking capacity of patients with moderate intermittent claudication. DATA SOURCES: A search of MEDLINE for trials published between 1976 and 1994 inclusive, and a bibliographic review of all articles retrieved. STUDY SELECTION: Randomized, placebo-controlled, double-blind clinical trials were selected that evaluated the pain-free walking distance (the distanced walked on a treadmill before the onset of calf pain) and the absolute claudication distance (the maximum distance walked on a treadmill) among patients with moderate intermittent claudication. Twelve study groups in 11 trials were included in the analysis. DATA EXTRACTION: In addition to information regarding the trial design, patient characteristics, dosages and treatment periods, the means and standard deviations were collected for both the pain-free walking and absolute claudication distances. Trial quality was also assessed. DATA SYNTHESIS: Overall, there was a statistically significant improvement in the pain-free walking distance after pentoxifylline therapy (weighted mean difference 29.4 m [95% confidence interval (CI) 13.0 to 45.9 m]); this finding was based on a total sample of 612 patients (308 in the treatment groups and 304 in the control groups). A significant improvement was also noted in the absolute claudication distance (weighted mean difference 48.4 m [95% CI 18.3 to 78.6 m]); this was based on a total sample of 511 patients (258 in the treatment group and 253 in the control group). In a sensitivity analysis of the pain-free walking distance, significant treatment effects and no statistically significant heterogeneity were found when only trials were included that were "medically eligible" (involved patients with stage II disease and a pain-free walking distance of 50 to 200 m). In a similar sensitivity analysis of the absolute claudication distance, the two conditions resulting in a significant treatment effect and no significant heterogeneity were the inclusion of "medically eligible" trials and those with a shorter treatment duration (13 weeks or less). CONCLUSION: Pentoxifylline therapy may be efficacious in improving the walking capacity of patients with moderate intermittent claudication. However, properly conducted clinical trials are required to provide a true estimate of the benefit.     

New antiepileptic drugs. Overcoming the limitations of traditional therapy

Several new antiepileptic drugs have become available recently. Since seizures and epilepsy are common, primary care physicians are likely to encounter a patient who is taking one of these new medications. Successful medical management of epilepsy requires a proper understanding of medication half-life, indications, and side effects. Felbamate has a broad spectrum of efficacy but is limited by side effects and idiosyncratic reactions. Fosphenytoin has the efficacy of phenytoin and offers the advantage of intramuscular and intravenous dosing without the significant adverse effects associated with intravenous phenytoin; however, it is expensive. Gabapentin has minimal side effects and drug interactions yet has limited efficacy for seizures. Lamotrigine has broad seizure efficacy but requires a slow adjustment to therapeutic levels. Topiramate has minimal drug interactions, but therapy must be initiated slowly to avoid side effects. All of the new antiepileptics hold great promise in the management of patients with recurrent seizures.     

Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials

CONTEXT: Aspirin has been widely used to prevent myocardial infarction and ischemic stroke but some studies have suggested it increases risk of hemorrhagic stroke. OBJECTIVE: To estimate the risk of hemorrhagic stroke associated with aspirin treatment. DATA SOURCES: Studies were retrieved using MEDLINE (search terms, aspirin, cerebrovascular disorders, and stroke), bibliographies of the articles retrieved, and the authors' reference files. STUDY SELECTION: All trials published in English-language journals before July 1997 in which participants were randomized to aspirin or a control treatment for at least 1 month and in which the incidence of stroke subtype was reported. DATA EXTRACTION: Information on country of origin, sample size, duration, study design, aspirin dosage, participant characteristics, and outcomes was abstracted independently by 2 authors who used a standardized protocol. DATA SYNTHESIS: Data from 16 trials with 55462 participants and 108 hemorrhagic stroke cases were analyzed. The mean dosage of aspirin was 273 mg/d and mean duration of treatment was 37 months. Aspirin use was associated with an absolute risk reduction in myocardial infarction of 137 events per 10000 persons (95% confidence interval [CI], 107-167; P<.001) and in ischemic stroke, a reduction of 39 events per 10000 persons (95% CI, 17-61; P<.001). However, aspirin treatment was also associated with an absolute risk increase in hemorrhagic stroke of 12 events per 10000 persons (95% CI, 5-20; P<.001). This risk did not differ by participant or study design characteristics. CONCLUSIONS: These results indicate that aspirin therapy increases the risk of hemorrhagic stroke. However, the overall benefit of aspirin use on myocardial infarction and ischemic stroke may outweigh its adverse effects on risk of hemorrhagic stroke in most populations.     

The efficacy of motivational interviewing: A meta-analysis of controlled clinical trials.

A meta-analysis was conducted on controlled clinical trials investigating adaptations of motivational interviewing (AMIs), a promising approach to treating problem behaviors. AMIs were equivalent to other active treatments and yielded moderate effects (from .25 to .57) compared with no treatment and/or placebo for problems involving alcohol, drugs, and diet and exercise. Results did not support the efficacy of AMIs for smoking or HIV-risk behaviors. AMIs showed clinical impact, with 51% improvement rates, a 56% reduction in client drinking, and moderate effect sizes on social impact measures (d=0.47). Potential moderators (comparative dose, AMI format, and problem area) were identified using both homogeneity analyses and exploratory multiple regression. Results are compared with other review results and suggestions for future research are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of psychotherapeutic treatments for PTSD: a meta-analysis of controlled clinical trials

This meta-analysis synthesized the results from controlled, clinical trials of psychotherapeutic treatments for posttraumatic stress disorder (PTSD). Psychotherapeutic modalities included behavioral, cognitive, and psychodynamic treatments, in group and individual settings. Participants in the studies included combat veterans from the Vietnam and Lebanon Wars, crime-related victims, and severe bereavement sufferers. The impact of psychotherapy on PTSD and psychiatric symptomatology was significant, d = .52, r = .25, when measured immediately after treatments were administered. Similarly, there was no decay in the effect of treatment at follow-up, d = .64, r = .31. Moreover, for target symptomes of PTSD and general psychological symptomes (intrusion, avoidance, hyperarousal, anxiety, and depression), effect sizes were significant, ranging from r's of .2-.49. Results suggest substantial promise for improving psychological health and decreasing related symptoms for those suffering from PTSD.     

The health and welfare effects of day-care: a systematic review of randomised controlled trials

The large scale production of recombinant hemoglobin (Hb) from microorganism or transgenic hosts for Hb-based blood substitutes places utmost emphasis on purity. In the present study, a high-resolution, convenient and inexpensive purification method is developed for purification of Hb from mixtures containing E. coli extract and bovine serum. This method is based on affinity elution by pyrophosphate (PPi) of Hb adsorbed on an FPLC column of the anion exchanger Toyopearl DEAE-650M. Compared to pH elution or NaCl elution, PPi elution makes possible the preparation of Hb of much higher purity. A procedure combining pH elution and PPi elution sequentially using a single column proves particularly valuable. The purification method is also applicable to the purification of cyanomet-Hb (CNHb+).     

Randomized controlled trials

Acid trehalase (AT) has always been reported to be copurified with invertase (I) and a 40 kDa additional protein. Glucose grown stationary phase cells of Saccharomyces cerevisiae contained least I activity. So, it was attempted to purify AT from these cells (I:AT = 10.83). Studies on specific activity, percent recovery and I:AT ratio of different pools, collected during purification of AT, indicated that samples containing ratio I:AT < 2.2 were unstable. Purification methodology favouring association (DEAE-Sephadex chromatography) resulted in gaining total activity while methodology favouring dissociation (HPGPLC) resulted in tremendous loss in recovery. Active pool (Pool 1X) appeared to be electrophoretically homogeneous but dissociated into 175, 90, 68, 61, 57 (minor bands) and 37-41 (major band) molar mass (kDa) bands on SDS-PAGE. Inactive pools (Pools 1Y, 3X, 3Y) did not contain the 37-41 kDa major band. So, association of both I and a 37-41 kDa protein with AT appeared to be essential. Two bands of isoelectric pH (pI) 4.6 and 4.7 were present in pool 1X enzyme preparation. All SDS-PAGE-resolved bands of pool 1X, in an average, contained high aspartate/asparagine and low cysteine residues. AT activity appeared to be highly sensitive to the change in pH and also to agents affecting ionisation of protein, e.g., betaine, NaCl, acetate, etc. Association of AT components in presence of NaCl was demonstrated spectrophotometrically. Specific activity of AT decreased with dilution. Substrate mediated allosterism for this enzyme preparation suggested that AT existed as an equilibrium mixture of protomer-oligomer. It was suggested that reversible association-dissociation was a mechanism for the regulation of AT activity.     

Effect of reduced dietary sodium on blood pressure: a meta-analysis of randomized controlled trials

OBJECTIVE:- To ascertain whether restriction of dietary sodium lowers blood pressure in hypertensive and normotensive individuals. DATA SOURCES:- An English-language computerized literature search, restricted to human studies with Medical Subject Heading terms, "hypertension," "blood pressure," "vascular resistance," "sodium and dietary," "diet and sodium restricted," "sodium chloride," "clinical trial," "randomized controlled trial," and "prospective studies," was conducted. Bibliographies of review articles and personal files were also searched. TRIAL SELECTION:- Trials that had randomized allocation to control and dietary sodium intervention groups, monitored by timed sodium excretion, with outcome measures of both systolic and diastolic blood pressure were selected by blinded review of the methods section. DATA EXTRACTION:- Two observers extracted data independently, using purpose-designed forms, and discrepancies were resolved by discussion. DATA SYNTHESIS:- The 56 trials that met our inclusion criteria showed significant heterogeneity. Publication bias was also evident. The mean reduction (95% confidence interval) in daily urinary sodium excretion, a proxy measure of dietary sodium intake, was 95 mmol/d (71-119 mmol/d) in 28 trials with 1131 hypertensive subjects and 125 mmol/d (95-156 mmol/d) in 28 trials with 2374 normotensive subjects. After adjustment for measurement error of urinary sodium excretion, the decrease in blood pressure for a 100-mmol/d reduction in daily sodium excretion was 3.7 mm Hg (2.35-5.05 mm Hg) for systolic (P<.001) and 0.9 mm Hg (-0.13 to 1.85 mm Hg) for diastolic (P=.09) in the hypertensive trials, and 1.0 mm Hg (0.51-1.56 mm Hg) for systolic (P<.001) and 0.1 mm Hg (-0.32 to 0.51 mm Hg) for diastolic (P=.64) in the normotensive trials. Decreases in blood pressure were larger in trials of older hypertensive individuals and small and nonsignificant in trials of normotensive individuals whose meals were prepared and who lived outside the institutional setting. CONCLUSION:- Dietary sodium restriction for older hypertensive individuals might be considered, but the evidence in the normotensive population does not support current recommendations for universal dietary sodium restriction.