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PubMed2004

Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding.

BACKGROUND: The decline in circulating oestrogen around the time of the menopause often induces unacceptable symptoms that affect the health and well being of women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and progestogen combinations) is an effective treatment for these symptoms. In women with an intact uterus, unopposed oestrogen may induce endometrial stimulation and increase the risk of endometrial hyperplasia and carcinoma. The addition of progestogen reduces this risk but may cause unacceptable symptoms, bleeding and spotting which can affect adherence to therapy. OBJECTIVES: The objective of this review is to assess which hormone replacement therapy regimens provide effective protection against the development of endometrial hyperplasia and/or carcinoma with a low rate of abnormal vaginal bleeding. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966 to January 2003), EMBASE (1980 to January 2003), Current Contents (1993 to January 2003), Biological Abstracts (1969 to 2002), Social Sciences Index (1980 to January 2003), PsycINFO (1972 to February 2003) and CINAHL (1982 to January 2003). The search strategy was developed by the Cochrane Menstrual Disorder and Subfertility Group. Attempts were also made to identify trials from citation lists of review articles and drug companies were contacted for unpublished data. In most cases, the corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of unopposed oestrogen therapy, combined continuous oestrogen-progestogen therapy and sequential oestrogen-progestogen therapy with each other and placebo administered over a minimum treatment period of six months. Trials had to assess which regimen was the most protective against the development of endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular bleeding. DATA COLLECTION AND ANALYSIS: Sixty RCTs were identified. Of these 23 were excluded and seven remain awaiting assessment. The reviewers assessed the thirty included studies for quality, extracted the data independently and odds ratios for dichotomous outcomes were estimated. Outcomes analysed included frequency of endometrial hyperplasia or carcinoma, frequency of irregular bleeding and unscheduled biopsies or dilation and curettage, and adherence to therapy. MAIN RESULTS: Unopposed moderate or high dose oestrogen therapy when compared to placebo was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment and follow up. Odds ratios ranged from (1 RCT; OR 5.4, 95% CI 1.4 to 20.9) for 6 months of treatment to (4 RCTs; OR 9.6, 95% CI 5.9 to 15.5) for 24 months treatment and (1 RCT; OR 15.0, 95% CI 9.3 to 27.5) for 36 months of treatment with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those who took placebo). Irregular bleeding and non adherence to treatment were also significantly more likely under these unopposed oestrogen regimens that increased bleeding with higher dose therapy. Although not statistically significant, there was a 3% incidence (2 RCTs) of hyperplasia in women who took low dose oestrogen compared to no incidence of hyperplasia in the placebo group. The addition of progestogens, either in continuous combined or sequential regimens, helped to reduce the risk of endometrial hyperplasia and improved adherence to therapy. At longer duration of treatment, continuous therapy was more effective than sequential therapy in reducing the risk of endometrial hyperplasia. There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every three months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of t in any of the treatment groups during the duration (maximum of six years) of these trials. During the first year of therapy irregular bleeding and spotting was more likely in continuous combined therapy than sequential therapy. However, during the second year of therapy bleeding and spotting was more likely under sequential regimens. REVIEWERS' CONCLUSIONS: There is strong and consistent evidence in this review that unopposed oestrogen therapy, at moderate and high doses, is associated with increased rates of endometrial hyperplasia, irregular bleeding and consequent non adherence to therapy. The addition of oral progestogens administered either sequentially or continuously is associated with reduced rates of hyperplasia and improved adherence to therapy. Irregular bleeding is less likely under sequential than continuous therapy during the first year of therapy but there is a suggestion that continuous therapy over long duration is more protective than sequential therapy in the prevention of endometrial hyperplasia. Hyperplasia is more likely when progestogen is given every three months in a sequential regimen compared to a monthly progestogen sequential regimen.

Endometrial Hyperplasia↗

PubMed2000

Depot haloperidol decanoate for schizophrenia.

BACKGROUND: The mainstay of treatment for schizophrenia is the antipsychotic group of drugs. These are usually given orally but compliance with medication given by this route may be difficult to quantify. Problems with treatment adherence are common. The development of depot injections in the 1960s gave rise to their extensive use as a means of long-term maintenance treatment. Haloperidol decanoate is one depot drug available in clinical practice. OBJECTIVES: To assess the effects of haloperidol decanoate versus oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). References of all identified trials were also inspected for more studies. SELECTION CRITERIA: All relevant randomised trials focusing on people with schizophrenia where haloperidol decanoate, oral anti-psychotics or other depot preparations were compared. Outcomes such as death, clinically significant change in global function, mental state, relapse, hospital admission, adverse effects and acceptability of treatment were sought. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data Mantel-Haenszel odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. MAIN RESULTS: In a haloperidol decanoate versus placebo comparison, two small studies reported that significantly fewer people on depot left early (OR 0.09 CI 0.03-0.21, NNT 2 CI 1-3) or experienced no important improvement in mental state (OR 0. 04 CI 0.01-0.15). Zississ (1982) suggested that those taking haloperidol decanoate would need less additional antipsychotic medication (OR 0.14 Cl 0.04-0.55, NNT 2 CI 1-5). Haloperidol decanoate was compared to oral haloperidol in a single trial that showed no differences in global impression, mental state or side effects ( approximately approximately Zuardi 1983 approximately approximately , n=22). Compliance with medication was not reported in this study. Eight trials compared haloperidol decanoate to other depot neuroleptics and again no differences were found for the outcomes of death, global impression, mental state, behaviour, or side effects. REVIEWER'S CONCLUSIONS: Haloperidol decanoate may have a substantial effect in improving the symptoms and behaviour associated with schizophrenia in comparison to placebo, but data are remarkably sparse. There are no discernible differences between the depot form of haloperidol and its oral equivalent. For those needing and willing to take the drug, the means of administration is then a matter of individual choice and clinical judgement. As there are no clear differences between haloperidol decanoate and other depots, the choice of depot medication could also be individually tailored and patient preference exercised. Well-conducted and reported randomised trials are needed comparing haloperidol decanoate with other depots but the comparison of haloperidol decanoate to oral antipsychotics is a priority.

Antipsychotic Agents↗

PubMed1998

Control of expression of a gene encoding an extensin by phytochrome and a blue light receptor in spores of Adiantum capillus-veneris L.

In the present study, using a newly developed fluorescent differential display technique, we have carried out large-scale screening for genes whose expression was regulated by phytochrome and antagonistically by a blue light receptor in the spores of the fern Adiantum capillus-veneris L. Spores after imbibition were briefly irradiated with red, red/blue or blue light and collected 8 h after the irradiation. Total RNA was isolated from each sample and used to make cDNA with an oligo-dT primer. The cDNA was then used as a template for PCR with the oligo-dT primer and 80 arbitrary primers. The resulting PCR products were analyzed by an automated fluorescent DNA sequencer. Among 8000 displayed bands, we identified 15 up-regulated and four down-regulated bands by red light, and this red light effect was irreversibly reversed by blue light. We cloned one of the up-regulated cDNA fragments and used it to screen a cDNA library prepared from the spores. The isolated insert is predicted to encode Ser-(Pro)n repeats and showed homology with cell wall-associated extensins. The expression of this cDNA was induced 8 h after a red light treatment and the red light induction was photoreversibly prevented by far-red light and photoirreversibly by blue light. The mRNA of this gene was detectable 4 h after red light irradiation and gradually increased in germinating spores.

Amino Acid Sequence↗

PubMed2006

Generation, annotation and analysis of ESTs from Trichoderma harzianum CECT 2413.

BACKGROUND: The filamentous fungus Trichoderma harzianum is used as biological control agent of several plant-pathogenic fungi. In order to study the genome of this fungus, a functional genomics project called "TrichoEST" was developed to give insights into genes involved in biological control activities using an approach based on the generation of expressed sequence tags (ESTs). RESULTS: Eight different cDNA libraries from T. harzianum strain CECT 2413 were constructed. Different growth conditions involving mainly different nutrient conditions and/or stresses were used. We here present the analysis of the 8,710 ESTs generated. A total of 3,478 unique sequences were identified of which 81.4% had sequence similarity with GenBank entries, using the BLASTX algorithm. Using the Gene Ontology hierarchy, we performed the annotation of 51.1% of the unique sequences and compared its distribution among the gene libraries. Additionally, the InterProScan algorithm was used in order to further characterize the sequences. The identification of the putatively secreted proteins was also carried out. Later, based on the EST abundance, we examined the highly expressed genes and a hydrophobin was identified as the gene expressed at the highest level. We compared our collection of ESTs with the previous collections obtained from Trichoderma species and we also compared our sequence set with different complete eukaryotic genomes from several animals, plants and fungi. Accordingly, the presence of similar sequences in different kingdoms was also studied. CONCLUSION: This EST collection and its annotation provide a significant resource for basic and applied research on T. harzianum, a fungus with a high biotechnological interest.

Algorithms↗

PubMed1990

Government documents and the online catalog.

Prior to planning for implementing the NOTIS system, the Vanderbilt Medical Center Library had not fully cataloged its government publications, and records for these materials were not in machine-readable format. A decision was made that patrons should need to look in only one place for all library materials, including the Health and Human Services Department publications received each year from the central library's Government Documents Unit. Beginning in 1985, these publications were added to the library's database, and the entire 7,200-piece collection is now in the online catalog. Working with these publications has taught the library much about the advantages and disadvantages of cataloging government documents in an online environment. It was found that OCLC cataloging copy is eventually available for most titles, although only about 10% of the records have MeSH headings. Staff time is the major expenditure; problems are caused by documents' irregular nature, frequent format changes, and difficult authority work. Since their addition to the online catalog, documents are used more and the library has better control.

Cataloging↗

PubMed2006

Understanding SAGE data.

Serial analysis of gene expression (SAGE) is a method for identifying and quantifying transcripts from eukaryotic genomes. Since its invention, SAGE has been widely applied to analyzing gene expression in many biological and medical studies. Vast amounts of SAGE data have been collected and more than a thousand SAGE-related studies have been published since the mid-1990s. The principle of SAGE has been developed to address specific issues such as determination of normal gene structure and identification of abnormal genome structural changes. This review focuses on the general features of SAGE data, including the specificity of SAGE tags with respect to their original transcripts, the quantitative nature of SAGE data for differentially expressed genes, the reproducibility, the comparability of SAGE with microarray and the future potential of SAGE. Understanding these basic features should aid the proper interpretation of SAGE data to address biological and medical questions.

Data Interpretation, Statistical↗

PubMed2005

Environmental sanitary interventions for preventing active trachoma.

BACKGROUND: Trachoma is the second or third major cause of blindness. It is responsible for about six million blind people worldwide, mostly in the poor communities of developing countries. One of the major strategies advocated for the control of the disease is the application of various environmental sanitary measures to such communities. OBJECTIVES: To assess the evidence for the effectiveness of environmental sanitary measures on the prevalence of active trachoma in endemic areas. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1980 to January 2005), LILACS (April 2004), the reference list of trials and the Science Citation Index. We also contacted agencies, experts and researchers in trachoma control. SELECTION CRITERIA: This review included randomised and quasi-randomised controlled trials comparing any form of environmental hygiene measures with no measure. These hygienic measures included fly control, provision of water and health education. Participants in the trials were people normally resident in the trachoma endemic areas. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the quality of trials. Study authors were contacted for additional information. Three trials met the inclusion criteria but meta-analysis was not conducted due to heterogeneity of the studies. MAIN RESULTS: Two studies that assessed insecticide spray as a fly control measure found that trachoma is reduced by at least 55% to 61% with this measure compared to no intervention. One study found that another fly control measure, latrine provision, reduced trachoma by 29.5% compared to no intervention; this was, however, not statistically significantly different. Another study revealed that health education on personal and household hygiene reduced the incidence of trachoma such that the odds of reducing trachoma in the health education village was about twice that of the no intervention village. However, all the studies have some methodological concerns relating to concealment of allocation and non-consideration of clustering effect in data analysis. AUTHORS' CONCLUSIONS: There is evidence that insecticide spray as a fly control measure reduces trachoma significantly. Latrine provision as a fly control measure has not demonstrated significant trachoma reduction. Health education may be effective in reducing trachoma. There is a dearth of data to determine the effectiveness of all aspects of environmental sanitation in the control of trachoma.

Animals↗

PubMed2005

Trypanocidal drugs for late stage, symptomatic Chagas disease (Trypanosoma cruzi infection).

BACKGROUND: People with Chagas disease (American Trypanosomiasis) may develop progressive and potentially lethal heart conditions. Drugs to eliminate the causative parasite, Trypanosoma cruzi, currently in use have limited therapeutic value and are used in early stages of the disease. Extending the use of these drugs to treat symptomatic chronic parasitism with chronic Chagasic cardiopathy (CCC) and progressive dilated cardiomyopathy has been proposed. OBJECTIVES: To assess the effects (harms and benefits) of nitrofurans and imidazolic trypanocidal drugs for treating late stage chronic Chagas disease and CCC. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 3, 2004), MEDLINE (1985-2004), EMBASE (1985-2004), BIREME (1985-2004), LILACS (1985-2004), ARTEMISA (1985-2004), SCIELO (1985-2004). Indexing terms in English and Spanish were used. References obtained were assessed for relevance by two reviewers independently. SELECTION CRITERIA: We included randomized controlled clinical trials (RCTs), single or double blind using trypanocidal drugs versus placebo or no treatment in CCC. DATA COLLECTION AND ANALYSIS: All articles retrieved were assessed using a predefined check list to determine if they met the inclusion criteria. Two independent reviewers collected data using a pre-designed form piloted on three articles before the review process started. Disagreements were resolved by a third reviewer. If the information was unavailable the articles were excluded. We planned a quantitative analysis of reduction of parasite load whether recorded as a categorical variable or the reduction of specific antibody titers. However insufficient data were available for quantitative analysis. We prepared a qualitative description of data identified. MAIN RESULTS: We found only one randomized double blind placebo controlled trial. We also found six uncontrolled or non-randomized studies which were of some relevance and were therefore described. We found insufficient evidence to define the effects of drug treatment for people with CCC. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the efficacy of nitrofurans or imidazolic drugs as recommended treatment in CCC and chronic T.cruzi infections, specifically if overt heart disease is present. A well designed randomized controlled trial is necessary to establish if new drugs are suitable for treatment of cardiac patients with CCC.

Chagas Cardiomyopathy↗

PubMed2004

TIPS versus paracentesis for cirrhotic patients with refractory ascites.

BACKGROUND: Ten per cent of cirrhotic patients develop refractory ascites, which carries substantial morbidity and has a one-year survival of less than 50 per cent. Patients with refractory ascites may benefit from transjugular intrahepatic portosystemic stent-shunts (TIPS). OBJECTIVES: To compare TIPS versus paracentesis standard treatment in patients with refractory ascites due to cirrhosis with regard to overall short- and long-term mortality, treatment efficacy, and complications. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register (July 2003), The Cochrane Central Register of Controlled Trials on The Cochrane Library (Issue 1, 2003), MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), and CINAHL (1982 to July 2003). We supplemented the searches with reading through scientific citations, review of citations in relevant primary articles, and hand-searched abstracts from national meetings. SELECTION CRITERIA: We included randomised clinical trials comparing TIPS and paracentesis with or without volume expanders for cirrhotic patients with refractory ascites. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of the randomised clinical trials by the generation of the allocation section, allocation concealment, and follow-up. Two independent observers extracted data from each trial. We contacted trial authors for additional information. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI). MAIN RESULTS: Four randomised clinical trials, including 264 patients, met the inclusion criteria. Methodological quality was moderate. Thirty-day mortality (OR 1.00, 95% CI 0.10 to 10.06, P = 1.0) and 24-month mortality (OR 1.17, 95% CI 0.52 to 2.66, P = 0.70) did not differ significantly between TIPS and paracentesis treatment. TIPS significantly reduced ascites re-accumulation at three months (OR 0.07, 95% CI 0.03 to 0.18, P < 0.00001) and at 12 months follow-up (OR 0.14, 95% CI 0.06 to 0.28, P < 0.00001). Hepatic encephalopathy occurred significantly more often in the TIPS group (OR 2.11, 95% CI 1.22 to 3.66, P = 0.008). Gastrointestinal bleeding (OR 0.82, 95% CI 0.36 to 1.84, P = 0.63), acute renal failure (OR 0.64, 95% CI 0.15 to 2.72, P = 0.55), septicemia/infection (OR 1.05, 95% CI 0.22 to 4.94, P = 0.96), and disseminated intravascular coagulation (OR 0.82, 95% CI 0.26 to 1.84, P = 0.63) did not differ significantly between groups. REVIEWERS' CONCLUSIONS: TIPS removed ascites more effectively than paracentesis. After 12 months, the beneficial effects of TIPS on ascites was still present. Mortality, gastrointestinal bleeding, septicemia/infection, acute renal failure, and disseminated intravascular coagulation did not differ significantly between the two groups. Hepatic encephalopathy occurred significantly more often in the TIPS group.

Ascites↗

PubMed2002

A high-throughput Arabidopsis reverse genetics system.

A collection of Arabidopsis lines with T-DNA insertions in known sites was generated to increase the efficiency of functional genomics. A high-throughput modified thermal asymmetric interlaced (TAIL)-PCR protocol was developed and used to amplify DNA fragments flanking the T-DNA left borders from approximately 100000 transformed lines. A total of 85108 TAIL-PCR products from 52964 T-DNA lines were sequenced and compared with the Arabidopsis genome to determine the positions of T-DNAs in each line. Predicted T-DNA insertion sites, when mapped, showed a bias against predicted coding sequences. Predicted insertion mutations in genes of interest can be identified using Arabidopsis Gene Index name searches or by BLAST (Basic Local Alignment Search Tool) search. Insertions can be confirmed by simple PCR assays on individual lines. Predicted insertions were confirmed in 257 of 340 lines tested (76%). This resource has been named SAIL (Syngenta Arabidopsis Insertion Library) and is available to the scientific community at www.tmri.org.

Agrobacterium tumefaciens↗

PubMed2005

Depot perphenazine decanoate and enanthate for schizophrenia.

BACKGROUND: Antipsychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Perphenazine decanoate and enanthate are depot antipsychotics that belong to the phenothiazine family and have a piperazine ethanol side chain. OBJECTIVES: To assess the effects of depot perphenazine decanoate and enanthate versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: We updated previous searches of the Cochrane Schizophrenia Group Register (June 1998), Biological Abstracts (1982-1998), the Cochrane Library (Issue 2, 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) by searching the Cochrane Schizophrenia Group Register (March 2004). References of all identified trials were also inspected for more studies and industry contacted. SELECTION CRITERIA: We compared randomised clinical trials focusing on people with schizophrenia where depot perphenazine decanoate and enanthate, oral antipsychotics or other depot preparations. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them and extracted data. For dichotomous data we estimated the Relative Risk (RR) with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat. MAIN RESULTS: Only four studies (Ahlfors 1980, Eufe 1979, Knudsen 1985c, Tegeler 1979), randomising a total 313 people could be included in this review and this combined with an overall lack of usable data limits any interpretation of results. Perphenazine enanthate was not significantly any better or worse than other depot antipsychotics in most of the main outcomes such as global state, relapse or leaving the study early. We found some differences favouring the control groups for adverse effects. One study (Ahlfors 1980) of six months' duration (n=172), compared perphenazine enanthate to clopenthixol decanoate. There were no differences between the two groups for outcomes of global improvement, relapse and leaving the study early. More people in the perphenazine enanthate group, however, required anticholinergic drugs than those allocated to clopenthixol decanoate (RR 1.12 CI 1.0 to 1.2, NNT 10).A single study (n=64, duration six weeks) compared perphenazine enanthate and its longer acting decanoate ester. Data on relapse and leaving the study early failed to show convincing differences. The enanthate group, however, experienced more movement disorders (RR 1.36, CI 1.1 to 1.8 NNT 5) than those allocated the decanoate ester of the same drug and required more anticholinergic drugs (RR 1.47 CI 1.1 to 2.0, NNT 4). AUTHORS' CONCLUSIONS: Depot perphenazine is in clinical use in the Nordic countries, Belgium, Portugal and the Netherlands. At a conservative estimate, a quarter of a million people suffer from schizophrenia in those countries and could be treated with depot perphenazine. The total number of participants in the four trials with useful data is 313. None of the studies observed the effects of oral versus depot antipsychotic drugs. Until well conducted and reported randomised trials are undertaken clinicians will be in doubt as to the effects of perphenazine depots and people with schizophrenia should exercise their own judgement or ask to be randomised.

Antipsychotic Agents↗

PubMed2025

Chromatin Regulatory Targets for Anticancer Therapeutics.

Chromatin serves to organize and compact the genome but also functions as a signaling hub for the dynamic regulation of transcriptional programs that control cell type specification. The historical discovery that several pro-differentiation anti-cancer agents target chromatin regulatory enzymes buoyed early interest in developing drugs that modulate chromatin structure and function. Chromatin-based drug discovery has since flourished alongside major advances in discovery chemistry and target selection, producing a rich collection of chemical probes, drugs, and drug candidates targeting chromatin regulatory processes. The substantial growth and maturity of this field over the last several decades provides an opportunity to reflect on the successes and failures associated with translating chromatin regulatory targets into anti-cancer drugs. Taking a target-centric perspective, we discuss the motivation for pursuing specific chromatin regulatory proteins and review the chemistries that enabled small molecule discovery and development. In so doing, we hope to evaluate the strength of these targets, the agents that prosecute them, and the prospects for future efforts in this field.

Humans↗

PubMed2005

Cleavage stage versus blastocyst stage embryo transfer in assisted conception.

BACKGROUND: In the past decade, advances in the understanding of nutrient requirements of embryos, has led to the evolution of culture media designed to support extended culture of embryos in vitro from the standard procedure of 2 to 3 days (for early cleavage embryo transfer) to 5 to 6 days (blastocyst culture). The rationale for blastocyst culture is to improve the synchronicity of uterine and embryonic development and provide a mechanism for self-selection of viable embryos. Since the initial widespread introduction of blastocyst culture in 1998, there has been conflicting reports about the clinical benefits of this technique. OBJECTIVES: To determine if blastocyst stage embryo transfers (ETs) affects success rates compared with cleavage stage ETs and investigate what factors may influence this. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials. We also searched the Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. Attempts were made to identify trials from the National Research Register, the Clinical Trials Register and the citation lists of review articles and included trials. The last search date was May 2005. The first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. DATA COLLECTION AND ANALYSIS: Of the 45 trials that were identified, 16 trials met the inclusion criteria and were reviewed. Primary outcomes were rates of live birth, clinical pregnancy and multiple-pregnancy rates per couple. Secondary outcomes were rates of miscarriage, failure to transfer embryos, freezing, implantation and high order pregnancy and per cycle data. Quality assessment and data extraction were performed independently by two review authors. Meta-analysis was performed using odds ratios (OR) for dichotomous outcomes and weighted mean differences for binary outcomes with 95% confidence intervals (CI). MAIN RESULTS: There was no evidence of a difference in live-birth rate per couple between the two treatment groups (7 RCTs; OR 1.16, 95% CI 0.74 to 1.44 [Day 2/3 34.3% vs. Day 5/6 35.4%]); in the clinical pregnancy rate per couple (15 RCTs; OR 1.05, 95% CI 0.88 to 1.26 [Day 2/3 38.8% vs. 40.3%]) even for good prognosis patients (6 RCTs: OR 96% 1.06 CI 0.83 to 1.34). There was also no difference in multiple-pregnancy rate per couple (12 RCTs; OR 0.85, 95% CI 0.63 to 1.13) particularly in trials where equal numbers of embryos were transferred in both groups (6 RCTs: OR 0.91, 95% CI 0.63 to 1.32). There was no evidence of a difference in high order multiple-pregnancy rates per couple (5 RCTs; OR 0.44, 95% CI 0.15 to 1.33) or miscarriage rate per couple between the two groups (9 RCTs; OR 1.33, 95% CI 0.89 to 2.01). Rates of embryo freezing per couple was significantly higher in Day 2 to 3 transfers (9 RCTs; OR 0.45, 95% CI 0.36 to 0.57). Failure to transfer any embryos per couple was significantly higher in the Day 5 to 6 group (10 RCTs: OR 3.21, 95% CI 2.15 to 4.81[Day 2/3 3.5% vs D 5/6 10.1%]), but was not significantly different for good prognosis patients (7RCTs, OR 1.58 95% CI 0.65 to 3.82). AUTHORS' CONCLUSIONS: There is no evidence of a difference in live birth or pregnancy outcomes between Day 2 to 3 and Day 5 to 6 transfer of embryos. Blastocyst transfer was associated with an increase in failure to transfer any embryos in a cycle and a decrease in embryo freezing rates. In the absence of data on cumulative live birth rates resulting from fresh and thawed cycles, it is not possible to determine if this represents an advantage or disadvantage.

Blastocyst↗

PubMed2002

Perioperative fluid volume optimization following proximal femoral fracture.

BACKGROUND: Proximal Femoral Fracture (PFF) or 'hip fracture' is a frequent injury, and adverse outcomes are common. Many patients are elderly, with significant comorbidity. Several factors suggest the importance of developing appropriate techniques to optimize intravascular fluid volume. These may include protocols that enhance the efficacy of clinicians' assessments, invasive techniques such as oesophageal Doppler or central venous pressure monitoring, or advanced non-invasive techniques such as plethysmographic pulse volume determination. OBJECTIVES: To determine the optimal method of fluid volume optimization for adult patients undergoing surgical repair of hip fracture. Comparisons of fluid types (e.g. crystalloid vs. colloid) or of blood transfusion strategies or of other pharmacological interventions (e.g. inotropes) are not considered in this review. SEARCH STRATEGY: Randomized controlled trials (RCTs) since 1985 were identified by searching MEDLINE, EMBASE, the Cochrane Library, the Cochrane Anaesthesia Group's specialized Controlled Trials Register and bibliographies of retrieved articles. Relevant journals and conference proceedings were handsearched. SELECTION CRITERIA: RCTs comparing a fluid optimization intervention with normal practice (control) or with another fluid optimization intervention, in patients following PFF undergoing surgery of any type under anaesthesia of any type. DATA COLLECTION AND ANALYSIS: Searches and exclusion of clearly irrelevant articles were performed by one reviewer. Two reviewers examined independently the remaining studies, extracting study quality and results data. A wide range of short- and long-term outcome data was sought. Study quality was assessed using a ten-point instrument and studies were excluded if they did not meet the study criteria or if results were likely to be biased. Due to a lack of consistency in reporting, combination of data was not generally possible. MAIN RESULTS: Searches identified only four trials, of which two studies, randomizing a total of 130 patients, were of adequate quality and addressed the review question. Both studies were of invasive advanced haemodynamic monitoring during the intraoperative period only. One study randomized patients to 'normal care' or optimization using oesophageal Doppler; the second study randomized patients to 'normal care', oesophageal Doppler or central venous pressure monitoring. In each study, invasive monitoring led to a significant increase in volume of fluid infused and a reduction in length of hospital stay. The pooled Peto odds ratio for in-hospital fatality was 1.44 (95% confidence interval 0.45-4.62). Neither study followed patients beyond hospital discharge or assessed functional outcomes (for example return to previous accommodation). No serious complications were reported to be directly attributable to the monitoring interventions. There were no studies of protocol-guided fluid optimization or of advanced non-invasive techniques. REVIEWER'S CONCLUSIONS: Invasive methods of fluid optimization during surgery may shorten hospital stay, but their effects on other important, patient-centred, longer-term outcomes are uncertain. An adverse effect on fatality cannot be excluded. Other fluid optimization techniques have not been evaluated. The lack of randomized studies of adequate quality addressing this important question is disappointing given the high incidence and frequently adverse outcome of PFF. More research is needed.

Blood Volume↗

PubMed2004

Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age.

BACKGROUND: Pneumonia, most commonly caused by Streptococcus pneumoniae (Pnc), is a major cause of morbidity and mortality among young children especially in developing countries. Recently, the prevalence of antibiotic-resistant Pnc has increased worldwide such that the effectiveness of preventive strategies, like the new pneumococcal conjugate vaccines (PCV) on rates of invasive pneumococcal disease (IPD) and pneumonia, needs to be evaluated. OBJECTIVES: To determine the efficacy of PCV in reducing the incidence of IPD due to vaccine serotypes (VT) and x-ray confirmed pneumonia with consolidation of unspecified etiology in children who received PCV before 12 months of age. SEARCH STRATEGY: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2004), MEDLINE (1990 to March 2004) and EMBASE (1990 to December 2003). Reference list of articles, and books of abstracts of relevant symposia, were hand searched. Researchers in the field were also contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, among children below two years with IPD and clinical/radiographic pneumonia as outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently identified eligible studies, assessed trial quality, and extracted data. Differences were resolved by discussion. The inverse variance method was used to pool effect sizes. MAIN RESULTS: We identified four trials assessing the efficacy of PCV in reducing the incidence of IPD, two on x-ray confirmed pneumonia as outcome, and one on clinical pneumonia, with or without x-ray confirmation. Results from pooling HIV-1 negative children from the South African study with the other studies were as follows: the pooled vaccine efficacy (VE) for vaccine-type IPD was 88% (95% confidence interval (CI) 73% to 94%; fixed effect and random effects models), the effect measure was statistically significant (p <0.00001) and there was no heterogeneity (p = 0.77I2 0%); the pooled VE for all-serotype IPD was 66% (95% CI 46% to 79%; fixed effect model), the effect measure was statistically significant (p <0.00001) and there was no statistical heterogeneity (p = 0.09, I2 51%); the pooled VE for x-ray confirmed pneumonia was 22% (95% CI 11% to 31%; both fixed effect and random effects models) and there was no statistical heterogeneity (p = 0.80, I2 0%). Analyses that included all the children in the South African study (HIV-1 negative and HIV-1 positive children) and pooled with data from the other studies gave very similar results. REVIEWERS' CONCLUSIONS: PCV is effective in reducing the incidence of IPD from all serotypes but exerts a greater effect in reducing VT IPD. Although PCV is also effective in reducing the incidence of x-ray confirmed pneumonia, there are still uncertainties about the definition of this outcome. Additional randomised controlled trials are currently in progress.

Humans↗

PubMed2005

Reconstruction of large phylogenetic trees: a parallel approach.

Reconstruction of phylogenetic trees for very large datasets is a known example of a computationally hard problem. In this paper, we present a parallel computing model for the widely used Multiple Instruction Multiple Data (MIMD) architecture. Following the idea of divide-and-conquer, our model adapts the recursive-DCM3 decomposition method [Roshan, U., Moret, B.M.E., Williams, T.L., Warnow, T, 2004a. Performance of suptertree methods on various dataset decompositions. In: Binida-Emonds, O.R.P. (Eds.), Phylogenetic Supertrees: Combining Information to Reveal the Tree of Life, vol. 3 of Computational Biology, Kluwer Academics, pp. 301-328; Roshan, U., Moret, B.M.E., Williams, T.L., Warnow, T., 2004b. Rec-I-DCM3: A Fast Algorithmic Technique for reconstructing large phylogenetic trees, Proceedings of the IEEE Computational Systems Bioinformatics Conference (ICSB)] to divide datasets into smaller subproblems. It distributes computation load over multiple processors so that each processor constructs subtrees on each subproblem within a batch in parallel. It finally collects the resulting trees and merges them into a supertree. The proposed model is flexible as far as methods for dividing and merging datasets are concerned. We show that our method greatly reduces the computational time of the sequential version of the program. As a case study, our parallel approach only takes 22.1h on four processors to outperform the best score to date (Found at 123.7h by the Rec-I-DCM3 program [Roshan, U., Moret, B.M.E., Williams, T.L., Warnow, T, 2004a. Performance of suptertree methods on various dataset decompositions. In: Binida-Emonds, O.R.P. (Eds.), Phylogenetic Supertrees: Combining Information to Reveal the Tree of Life, vol. 3 of Computational Biology, Kluwer Academics, pp. 301-328; Roshan, U., Moret, B.M.E., Williams, T.L., Warnow, T., 2004b. Rec-I-DCM3: A Fast Algorithmic Technique for reconstructing large phylogenetic trees, Proceedings of the IEEE Computational Systems Bioinformatics Conference (ICSB)] on one dataset. Developed with the standard message-passing library, MPI, the program can be recompiled and run on any MIMD systems.

Journal Article↗

PubMed2004

Chitinase gene sequences retrieved from diverse aquatic habitats reveal environment-specific distributions.

Chitin is an abundant biopolymer whose degradation is mediated primarily by bacterial chitinases. We developed a degenerate PCR primer set to amplify a approximately 900-bp fragment of family 18, group I chitinase genes and used it to retrieve these gene fragments from environmental samples. Clone libraries of presumptive chitinase genes were created for nine water and six sediment samples from 10 aquatic environments including freshwater and saline lakes, estuarine water and sediments, and the central Arctic Ocean. Putative chitinase sequences were also retrieved from the Sargasso Sea metagenome sequence database. We were unable to obtain PCR product with these primers from an alkaline, hypersaline lake (Mono Lake, California). In total, 108 partial chitinase gene sequences were analyzed, with a minimum of 5 and a maximum of 13 chitinase sequences obtained from each library. All chitinase sequences were novel compared to previously identified sequences. Intralibrary sequence diversity was low, while we found significant differences between libraries from different water column samples and between water column and sediment samples. However, identical sequences were retrieved from samples collected at widely distributed locations that did not necessarily represent similar environments, suggesting homogeneity of chitinoclastic communities between some environments.

Amino Acid Sequence↗

PubMed2003

Open general medical wards versus specialist psychiatric units for acute psychoses.

BACKGROUND: As international healthcare policy has moved away from treating people with severe mental illness in large inpatient psychiatric institutions, beds for people with acute psychiatric disorders are being established in specialised psychiatric units in general hospitals. In developing countries, however, limited resources mean that it is not always possible to provide discrete psychiatric units, either in general hospitals or in the community. An alternative model of admission, used in the Caribbean, is to treat the person with acute psychosis in a general hospital ward. OBJECTIVES: To compare the outcomes for people with acute psychoses who have been admitted to open medical wards with those admitted to conventional psychiatric units. SEARCH STRATEGY: The Cochrane Schizophrenia Group's study-based register was searched (November 2001). This register is compiled from searches of BIOSIS, CINAHL, The Cochrane Library, EMBASE, LILACS, MEDLINE, PsycINFO, PSYNDEX, Sociofile, and many conference proceedings. SELECTION CRITERIA: All relevant randomised or quasi-randomised trials, allocating anyone thought to be suffering from an acute psychotic episode to either acute management on general medical wards, or acute management in a specialist psychiatric unit. The primary outcomes of interest were length of stay in hospital and relapse. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, assessed for quality, and their data would have been extracted. Homogeneous data were to have been synthesised. For binary data, the risk ratios (RR) and 95% confidence intervals (CI) were to have been calculated on an-intention-to-treat basis. If possible, the number needed to treat/harm statistic (NNT/H) was to have been calculated. For continuous data, weighted mean differences (WMD) were to have been calculated and only data from valid scales would have been reported in this review. MAIN RESULTS: We identified no relevant randomised trials. REVIEWER'S CONCLUSIONS: The Caribbean practice of treating people with severe mental illness on general medical wards has been influenced by socio-economic factors rather than evidence from randomised trials. This practice affords an opportunity for a well designed, well conducted and reported randomised trial, now impossible in many other settings.

Acute Disease↗