Objectives: To analyze sources searched in Cochrane reviews, to determine the proportion of trials included in reviews that are indexed in major databases, and to compare the quality of these trials with those from other sources.Methods: All new systematic reviews in the Cochrane Library, Issue1 2001, that were restricted to randomized controlled trials (RCTs) or quasi-RCTs were selected. The sources searched in the reviews were recorded, and the trials included were checked to see whether they were indexed in four major databases. Trials not indexed were checked to determine how they could be identified. The quality of trials found in major databases was compared with those found from other sources.Results: The range in the number of databases searched per review ranged between one and twenty-seven. The proportion of the trials in the four databases were Cochrane Controlled Trials Register=78.5%, MEDLINE=68.8%, Embase=65.0%, and Science/Social Sciences Citation Index=60.7%. Searching another twenty-six databases after Cochrane Controlled Trials Register (CCTR), MEDLINE, and Embase only found 2.4% additional trials. There was no significant difference between trials found in the CCTR, MEDLINE, and Embase compared with other trials, with respect to adequate allocation concealment or sample size.Conclusions: There was a large variation between reviews in the exhaustiveness of the literature searches. CCTR was the single best source of RCTs. Additional database searching retrieved only a small percentage of extra trials. Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials.

Literature searching for randomized controlled trials used in cochrane reviews: rapid versus exhaustive searches

Background
Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level with normal free thyroid hormones values. The prevalence of subclinical hypothyroidism is 4% to 8% in the general population, and up to 15% to 18% in women who are over 60 years of age. There is considerable controversy regarding the morbidity, the clinical significance of subclinical hypothyroidism and if these patients should be treated.

Objectives
To assess the effects of thyroid hormone replacement for subclinical hypothyroidism.

Search methods
We searched The Cochrane Library, MEDLINE, EMBASE and LILACS. Ongoing trials databases, reference lists and abstracts of congresses were scrutinized as well.

Selection criteria
All studies had to be randomised controlled trials comparing thyroid hormone replacement with placebo or no treatment in adults with subclinical hypothyroidism. Minimum duration of follow-up was one month.

Data collection and analysis
Two authors independently assessed trial quality and extracted data. We contacted study authors for missing or additional information.

Main results
Twelve trials of six to 14 months duration involving 350 people were included. Eleven trials investigated levothyroxine replacement with placebo, one study compared levothyroxine replacement with no treatment. We did not identify any trial that assessed (cardiovascular) mortality or morbidity. Seven studies evaluated symptoms, mood and quality of life with no statistically significant improvement. One study showed a statistically significant improvement in cognitive function. Six studies assessed serum lipids, there was a trend for reduction in some parameters following levothyroxine replacement. Some echocardiographic parameters improved after levothyroxine replacement therapy, like myocardial relaxation, as indicated by a significant prolongation of the isovolumic relaxation time as well as diastolic dysfunction. Only four studies reported adverse events with no statistically significant differences between groups.

Authors' conclusions
In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups. Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function.

Thyroid hormone replacement for subclinical hypothyroidism.

BACKGROUND Multiple myeloma is a disease characterized by the neoplastic proliferation of a clone of plasma cells that can lead to bone destruction. Bisphosphonates are specific inhibitors of osteoclastic activity. Therefore, there is a pharmacological basis for their use in multiple myeloma. However, the exact clinical role of bisphosphonates in multiple myeloma remains unclear. OBJECTIVES Primary: to determine whether adding bisphosphonates to standard therapy in multiple myeloma decreases skeletal-related morbidity (pathological fractures), skeletal-related mortality and overall mortality. Secondary: to determine the effects of bisphosphonates on pain, quality of life and incidence of hypercalcemia. SEARCH STRATEGY We searched MEDLINE (1966 - June 2001), LILACS (1982 - June 2001), EMBASE (1974 - December 2000) and the Cochrane Controlled Trials Register (all years, latest Issue 03/2001) to identify all randomized trials in multiple myeloma. All of these references were accessed in order to identify trials related to the use of bisphosphonates in myeloma. All relevant references in each article were also scanned. We also performed a handsearch of relevant meeting proceedings from 1993 to 2000. Additionally, manufacturers of bisphosphonates and researchers in the field were contacted. SELECTION CRITERIA Randomised trials with a parallel design on the use of bisphosphonate in myeloma compared with placebo or no treatment as a control group. DATA COLLECTION AND ANALYSIS Two reviewers independently assessed trial eligibility, methodological quality and abstracted data. A third reviewer checked all data after the extraction was completed. Statistical heterogeneity was tested using random and fixed effect models. All pooled data are reported using Peto odds ratios and, when appropriate, as absolute risk reduction and the number needed to treat to prevent or to cause a pathological event. MAIN RESULTS Eleven trials were included with 1113 patients analysed in bisphosphonates groups, and 1070 analysed in control groups. There was no significant statistical heterogeneity among trials for the endpoints selected for comparison in this review. The pooled analysis of the published evidence demonstrated the beneficial effect of bisphosphonates on prevention of pathological vertebral fractures [OR=0.59 (95% confidence interval (CI) 0.45-0.78); P=0.0001] and on amelioration of pain [OR = 0.59 (95%CI 0.46-0.76); P=0.00005]. However, the analysis of the effect of bisphosphonates on pain was based on clinically heterogeneous data and must be interpreted with caution. Although there was no statistical heterogeneity between groups, the benefit was most apparent with clodronate and pamidronate. In absolute terms, the result may be interpreted to mean that 10 (95%CI 7-20) patients with multiple myeloma should be treated to prevent one vertebral fracture, and 11 (95%CI 7-28) to prevent one patient experiencing pain. We found no significant effect of bisphosphonates on mortality, on the reduction of non-vertebral fractures or on the incidence of hypercalcemia. There were no significant adverse effects associated with the administration of bisphosphonates. Our results are based on the extraction of published data, which were sometimes poorly reported, and thus the results should be understood as the best possible summation of available evidence. REVIEWER'S CONCLUSIONS Adding bisphosphonates to the treatment of myeloma reduces pathological vertebral fractures and pain but - from the published evidence - not mortality. On current evidence, clodronate or pamidronate may be the preferred agents.

Bisphosphonates in multiple myeloma

Background
Mannitol is an osmotic agent and a free radical scavenger which might decrease oedema and tissue damage in stroke.

Objectives
To test whether treatment with mannitol reduces short and long-term case fatality and dependency after acute ischaemic stroke or intracerebral haemorrhage (ICH).

Search methods
We searched the Cochrane Stroke Group Trials Register (searched December 2006), MEDLINE (1966 to January 2007), the Chinese Stroke Trials Register (searched November 2006), the China Biological Medicine Database (searched December 2006) and the Latin-American database LILACS (1982 to December 2006). We also searched the database of Masters and PhD degree theses at Sao Paulo University (searched January 2007), and neurology and neurosurgery conference proceedings in Brazil from 1965 to 2006. In an effort to identify further published, ongoing and unpublished studies we searched reference lists and contacted authors of published trials.

Selection criteria
We included randomised controlled trials comparing mannitol with placebo or open control in patients with acute ischaemic stroke or non-traumatic intracerebral haemorrhage.

Data collection and analysis
Two review authors independently selected trials, assessed quality, extracted data, and performed the data analysis.

Main results
Three small trials, involving 226 participants, were included. One trial included patients with presumed ischaemic stroke without computerised tomography (CT) verification, and the other two trials included patients with CT-verified ICH. Data on the primary outcome measure (death and dependency) were not available in any of the trials. Death and disability could be calculated in the larger ICH trial without differences between the mannitol and control groups. Case fatality was not reported in the trial of ischaemic stroke. Case fatality did not differ between the mannitol and control groups in the ICH trials. Adverse events were either not found or not reported. The change in clinical condition was reported in two trials, and the proportion of those with worsening or not improving condition did not differ significantly between mannitol-treated patients and controls. Based on these three trials neither beneficial nor harmful effects of mannitol could be proved. Although no statistically significant differences were found between the mannitol-treated and control groups, the confidence intervals for the treatment effect estimates were wide and included both clinically significant benefits and clinically significant harms as possibilities.

Authors' conclusions
There is currently not enough evidence to support the routine use of mannitol in acute stroke patients. Further trials are needed to confirm or refute whether mannitol is beneficial in acute stroke.

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Mannitol for acute stroke

Background —Mannitol was reported to decrease cerebral edema associated with tissue damage and is used to treat acute stroke in many countries. Summary of Review —We tested whether there is any evidence from unconfounded randomized clinical trials that treatment with mannitol reduces short- and long-term case fatality and dependency if administered after ischemic stroke or cerebral parenchymal hemorrhage. Trials were identified by the standard search strategy of the Cochrane Collaboration Stroke Review Group. A supplementary MEDLINE search was performed, and the Chinese Stroke Trials Register and the Latin-American databank LILACS were checked. A search was performed of master’s and PhD degree theses in the databank of Sao Paulo University and in abstracts of medical congresses on neurology and neurosurgery during 1965–1997 in Brazil. Investigators were contacted for unpublished information. Only truly randomized unconfounded clinical trials were eligible for inclusion. Two of the reviewers independently extracted data from the trials. Data synthesis and analysis was performed with the use of the Cochrane Review Manager software (RevMan version 4.0.4). Conclusions —Only 1 trial fulfilled the inclusion criteria. The number of included patients was small, and the follow-up was short. Case fatality, the proportion of dependent patients, and side effects were not reported and were not available from the investigators. As a result of lack of appropriate randomized trials, currently no conclusion can be drawn on the effects of mannitol in acute stroke. The routine use of mannitol in all patients with acute stroke is not supported by evidence from randomized controlled clinical trials.

Cochrane report: A systematic review of mannitol therapy for acute ischemic stroke and cerebral parenchymal hemorrhage.

OBJECTIVE: To define and disseminate the optimal search strategy for clinical trials in the Latin American and Caribbean Health Science Literature (LILACS). This strategy was elaborated based on the optimal search strategy for MEDLINE recommended by Cochrane Collaboration for the identification of clinical trials in electronic databases. DESIGN: Technical information. SETTING: Clinical Trials and Meta-Analysis Unit, Federal University of Sao Paulo, in conjunction with the Brazilian Cochrane Center, Sao Paulo, Brazil. (http://www.epm.br/cochrane). DATA: LILACS/CD-ROM (Latin American and Caribbean Health Science Information Database), 27th edition, January 1997, edited by BIREME (Latin American and Caribbean Health Science Information Center). LILACS Indexes 670 journals in the region, with abstracts in English, Portuguese or Spanish; only 41 overlap in the MEDLINE-EMBASE. Of the 168.902 citations since 1982, 104,016 are in human trials, and 38,261 citations are potentiality clinical trials. Search strategy was elaborated combining headings with text word in three languages, adapting the interface of the LILACS. We will be working by locating clinical trials in LILACS for Cochrane Controlled Trials Database. This effort is being coordinated by the Brazilian Cochrane Center.

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Optimal search strategy for clinical trials in the Latin American and Caribbean Health Science Literature Database (LILACS).

/pdf/brief-communication-systematic-reviews-on-leptospirosis-1hpbmtor51.pdf

Aldemar Araujo Castro

Papers

Optimal search strategy for clinical trials in the Latin American and Caribbean Health Science Literature Database (LILACS).

Brief communication systematic reviews on leptospirosis