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PubMed2006

Cysteine, cystine or N-acetylcysteine supplementation in parenterally fed neonates.

BACKGROUND: L-cysteine is thought to be a conditionally essential (i.e., essential under certain conditions) amino acid for neonates. It is a precursor of glutathione, an antioxidant that may reduce oxidation injury. The addition of cysteine to parenteral nutrition (PN) allows for the reduction of the amount of methionine in PN, thereby limiting hepatotoxicity, and acidifies the solution, thereby increasing calcium and phosphate solubility, and potentially improving bone mineralization. OBJECTIVES: To determine the effects of supplementing parenteral nutrition with cysteine, cystine or its precursor N-acetylcysteine on neonatal growth and short and long-term outcomes. SEARCH STRATEGY: The standard search method of the Cochrane Neonatal Review Group was used. MEDLINE (1966-December 2005), EMBASE (1974-December 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006) and recent abstracts (until December 2005) from the Society for Pediatric Research/American Pediatric Society, Eastern Society for Pediatric Research, and Society for Parenteral and Enteral Nutrition were searched. SELECTION CRITERIA: All randomized (RCTs) and quasi-randomized trials that examined the effects of cysteine, cystine or N-acetylcysteine supplementation of neonatal PN were reviewed. Predetermined outcome variables included growth, nitrogen retention, mortality, morbidity secondary to oxidation injury, bone accretion, acidosis, liver disease, and cysteine levels. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Statistical analysis included relative risk, risk difference, and weighted mean difference (WMD). MAIN RESULTS: Six trials fulfilled entry criteria. The majority of patients in these trials were preterm. Five small trials evaluated short-term cysteine supplementation of cysteine-free PN. One large multicenter RCT evaluated short-term N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants (< or = 1000 grams). PRIMARY OUTCOMES: Growth was not significantly affected by cysteine supplementation (evaluated in one quasi-randomized trial) or by N-acetylcysteine supplementation (evaluated in one RCT). Nitrogen retention was significantly increased by cysteine supplementation (studied in four trials) (WMD 31.8 mg/kg/day, 95% confidence interval +8.2, +55.4, n = 95, including 73 preterm infants). SECONDARY OUTCOMES: Plasma levels of cysteine were significantly increased by cysteine supplementation but not by N-acetylcysteine supplementation. N-acetylcysteine supplementation did not significantly affect the risks of death by 36 postmenstrual weeks, bronchopulmonary dysplasia (BPD), death or BPD, retinopathy of prematurity (ROP), severe ROP, necrotizing enterocolitis requiring surgery, periventricular leukomalacia, intraventricular hemorrhage (IVH), or severe IVH. No data were available on other outcomes. AUTHORS' CONCLUSIONS: Available evidence from RCTs shows that routine short-term cysteine chloride supplementation of cysteine-free PN in preterm infants improves nitrogen balance.However, there is insufficient evidence to assess the risks of cysteine supplementation, especially regarding metabolic acidosis, which has been reported during the first two weeks of cysteine chloride administration. Available evidence from a large RCT trial does not support routine N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants. A large RCT would be required to assess whether routine prolonged cysteine supplementation of cysteine-free PN affects growth and short and long-term neonatal outcomes in very low birth weight infants.

Acetylcysteine↗
PubMed2004

Efficacy of topical non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis: meta-analysis of randomised controlled trials.

OBJECTIVE: To assess the efficacy of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of osteoarthritis. DATA SOURCES: Medline, Embase, Scientific Citation Index, CINAHL, Cochrane Library, and abstracts from conferences. REVIEW METHODS: Inclusion criterion was randomised controlled trials comparing topical NSAIDs with placebo or oral NSAIDs in osteoarthritis. Effect size was calculated for pain, function, and stiffness. Rate ratio was calculated for dichotomous data such as clinical response rate and adverse event rate. Number needed to treat to obtain the clinical response was estimated. Quality of trial was assessed, and sensitivity analyses were undertaken. RESULTS: Topical NSAIDs were superior to placebo in relieving pain due to osteoarthritis only in the first two weeks of treatment. Effect sizes for weeks 1 and 2 were 0.41 (95% confidence interval, 0.16 to 0.66) and 0.40 (0.15 to 0.65), respectively. No benefit was observed over placebo in weeks 3 and 4. A similar pattern was observed for function, stiffness, and clinical response rate ratio and number needed to treat. Topical NSAIDs were inferior to oral NSAIDs in the first week of treatment and associated with more local side effects such as rash, itch, or burning (rate ratio 5.29, 1.14 to 24.51). CONCLUSION: Randomised controlled trials of short duration only (less than four weeks) have assessed the efficacy of topical NSAIDs in osteoarthritis. After two weeks there was no evidence of efficacy superior to placebo. No trial data support the long term use of topical NSAIDs in osteoarthritis.

Administration, Topical↗
PubMed1998

Partially unfolded proteins efficiently penetrate cell membranes--implications for oral drug delivery.

We have previously reported on the biological activity of members of a library of low molecular weight compounds (carriers) that enable the oral delivery of proteins (Milstein, Proceedings of the 1995 Miami Bio/Technology Winter Symposium on Protein Engineering and Structural Biology, IRL Press at Oxford University Press, 1995, p. 13; Leone-Bay et al., J. Med. Chem. 38 (1995) 4263-4269; Leone-Bay et al., J. Med. Chem. 39 (1996) 2571-2578; [1-3]). When rats or primates are orally administered a solution of carrier and either recombinant human alpha-interferon (rhIFN), insulin or recombinant human growth hormone (rhGH) significant serum concentrations of the proteins are detectable. The transport activity of these compounds is positively correlated with their structural effects on the protein molecules. Direct measurement of the interaction of these carrier molecules with the proteins indicates that they reversibly destabilize the native state of the molecule favoring a partially unfolded conformation. Apparently these intermediate protein conformations are transport competent and are able to be absorbed through the intestinal tissue and into the bloodstream. Since the measured binding of the carriers to the partially unfolded proteins is relatively weak (Kb = 100 M(-1)) and the systemic activity of the proteins appears to be unaffected, the changes in the structure of the proteins are manifestly reversible.

Administration, Oral↗
PubMed1986

Pregnenolone 16 alpha-carbonitrile-inducible P-450 gene family: gene conversion and differential regulation.

A cytochrome P-450 cDNA clone, designated pP450PCN2, homologous to the previously characterized pregnenolone 16 alpha-carbonitrile (PCN)-induced P-450 cDNA (pP450PCN1; F. J. Gonzalez, D. W. Nebert, J. P. Hardwick, and C. B. Kasper, J. Biol. Chem. 260:7435-7441), was isolated from a rat liver cDNA expression library by use of a polyclonal anti-P450PCN1 antibody. This P-450 cDNA contains 2,014 base pairs and yields an open reading frame of a protein consisting of 504 amino acids (Mr = 57,760). P450PCN2 cDNA and protein shared 90% nucleotide and 89% amino acid similarity with P450PCN1 cDNA and protein, respectively. The 5' untranslated, coding, and 3' untranslated regions between the two cDNAs share 94, 93, and 79% similarities, respectively. Nucleotide differences in the coding regions, however, are not evenly distributed. Complete homology exists between the two mRNAs for 425 nucleotides (positions 346 through 771). Other regions of 93 nucleotides containing only one difference and 147 nucleotides containing two differences exist toward the 3' end of the coding regions. These data suggest the possibility that a gene conversion event(s) have occurred subsequent to duplication of the ancestral P450PCN gene. Oligonucleotide probes unique for P450PCN1 and P450PCN2 cDNAs were used to examine the levels of their respective mRNAs in noninduced and PCN-induced liver cells and in male and female rats of various ages. P450PCN1 mRNA was not detectable in either male or female rats at any ages. In contrast, P450PCN2 mRNA was present at a low level in newborn rats and became elevated in both males and females at 1 week of age. Levels of p450PCN2 mRNA continued to increase in males until 12 weeks, whereas the mRNA in females reached peak levels at 2 weeks of age but declined continuously at the onset of puberty (between 4 and 12 weeks). These levels of P45PCN2 mRNA closely parallel the increases in testosterone 6 beta-hydroxylase activity and P450PCN2 protein level, as analyzed by Western blots. P450PCN1 mRNA was induced by PCN, dexamethasone, and phenobarbital in both male and female rats. P450PCN2 mRNA was not significantly induced by PCN or dexamethasone but was readily induced by phenobarbital. Testosterone 6 beta-hydroxylase activity was also induced severalfold by PCN, dexamethasone, and phenobarbital. These data demonstrate that P450PCN1 and P450PCN2 genes are differentially regulated during development and after administration of inducing compounds and furthermore suggest that both enzymes possess testosterone 6 beta-hydroxylase activity.

Amino Acid Sequence↗
PubMed2004

Antibiotics for community acquired pneumonia in adult outpatients.

BACKGROUND: Community-acquired pneumonia (CAP) is a common condition representing a significant disease burden for the community, particularly for the elderly. Because antibiotics are helpful in treating CAP, they are the standard treatment and CAP thus contributes significantly to antibiotic use, which is associated with the development of bacterial resistance and side-effects. Although several studies have been published concerning CAP and its treatment, the available data arises mainly from studies conducted in hospitalized patients and outpatients. There is no concise summary of the available evidence that can help clinicians in choosing the most appropriate antibiotic. OBJECTIVES: Our goal was to summarize the evidence currently available from randomized controlled trials (RCTs) concerning the efficacy of alternative antibiotic treatments for CAP in ambulatory patients above 12 years of age. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2003) which contains the Cochrane Acute Respiratory Infections Group's trial register; MEDLINE (January 1966 to September week 3, 2003), and EMBASE (January 1974 to March 2003). Studies were also identified by checking the bibliographies of studies and review articles retrieved as well as by perusing medical journals. To identify any additional published or unpublished studies, we contacted the following antibiotics manufacturers: Abbott, AstraZeneca, Aventis, Boehringer-Ingelheim, Bristol-Myers-Squibb, GlaxoSmithKline, Hoffmann-LaRoche, Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Pharmacia, Sanofi, and Yamanouchi. No language restrictions were applied in any of the search strategies. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) in which one or more antibiotics were tested for the treatment of CAP in ambulatory adolescent or adult patients. Studies testing one or more antibiotic and reporting the diagnostic criteria used in selecting patients as well as the clinical outcomes achieved were included. No language restrictions were applied. DATA COLLECTION AND ANALYSIS: Data were extracted and study reports assessed by two independent reviewers (LMB and TJMV). Authors of studies were contacted as needed to resolve any ambiguities in the study reports. The data were analyzed using the Cochrane Collaboration's RevMan 4.2.2 Software. Differences between reviewers were resolved by discussion and consensus. MAIN RESULTS: Three randomized controlled trials involving a total of 622 patients aged 12 years and older diagnosed with community acquired pneumonia were included. The quality of the studies and of the reporting was variable. A variety of clinical, radiological and bacteriological diagnostic criteria and outcomes were reported. Overall there was no significant difference in the efficacy of the various antibiotics under study. REVIEWERS' CONCLUSIONS: Currently available evidence from RCTs is insufficient to make evidence-based recommendations for the choice of antibiotic to be used for the treatment of community acquired pneumonia in ambulatory patients. Pooling of study data was limited by the very low number of studies. Individual study results do not reveal significant differences in efficacy between various antibiotics and antibiotic groups. Multi-drug comparisons using similar administration schedules are needed to provide the evidence necessary for practice recommendations.

Adult↗
PubMed2006

Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants.

BACKGROUND: Hematocrit falls after birth in preterm infants due to physiological factors and frequent blood letting. Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia. OBJECTIVES: To assess the effectiveness and safety of early (before 8 days after birth) versus late (between 8 - 28 days after birth) initiation of EPO in reducing red blood cell transfusions in preterm and/or low birth weight infants. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2006) was searched. Electronic and manual searches were conducted in November 2005 of MEDLINE, EMBASE and CINAHL, personal files, bibliographies of identified trials and abstracts by the Pediatric Academic Societies' and the European Society of Pediatric Research Meetings published in Pediatric Research. SELECTION CRITERIA DESIGN: Randomized or quasi-randomized controlled trials. POPULATION: Preterm (< 37 weeks gestational age) or low birth weight infants (< 2500 g) less than eight days of age. INTERVENTION: Early initiation of EPO (initiated at < 8 days of age) vs. late initiation of EPO (initiated at 8 - 28 days of age). Outcomes; At least one of the following outcomes were reported: Use of one or more red blood cell transfusions; Total volume (ml/kg) of blood transfused per infant; Number of transfusions per infant; Number of donors to whom the infant was exposed; Mortality during initial hospital stay (all causes); and common outcomes associated with preterm birth. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Neonatal Review Group were followed independently by the authors to assess study quality and report outcomes. Weighted treatment effects, calculated using RevMan 4.2.8 included typical relative risk (RR), typical risk difference (RD), number needed to treat to benefit (NNTB), number needed to treat to harm (NNTH) and mean difference (MD), all with 95% confidence intervals (CI). A fixed effect model was used for meta-analyses. Heterogeneity tests including the I-squared (I(2)) test were performed to assess the appropriateness of pooling the data. MAIN RESULTS: Two high quality randomized double-blind controlled studies enrolling 262 infants were identified (Donato 2000; Maier 2002). Both studies used well defined, but not identical, criteria for blood transfusions. Between 14 and 32% of the enrolled infants had received blood transfusions prior to study entry. A non-significant reduction in the 'use one or more red blood cell transfusions' [typical RR 0.91 (95% CI 0.78, 1.06); typical RD - 0.07 (95% CI -0.18, 0.04)] favouring early EPO was noted. Both studies (n = 262) reported on "number of transfusions per infant"; early EPO administration resulted in a non-significant reduction compared to late EPO [typical WMD - 0.32 (95% CI -0.92, 0.29)]. There was no significant reduction in total volume of blood transfused per infant or in the number of donors to whom the infant was exposed. Retinopathy of prematurity (ROP) (all stages) was assessed in 191 infants. Early EPO led to a significant increase in the risk of ROP [(typical RR 1.40 (95% CI 1.05, 1.86); typical RD 0.16 (95% CI 0.03, 0.29); NNTH 6 (95% CI 3 -33)]. There was statistically significant heterogeneity for this outcome. Both studies (n = 191) reported on ROP stage > 3. No statistically significant increase in risk was noted [typical RR 1.56 (95% CI 0.71, 3.41); typical RD was 0.05 (95% CI - 0.04, 0.14)]. There was no statistically significant heterogeneity for this outcome for either RR or for RD. No other important favourable or adverse neonatal outcomes or side effects were reported. AUTHORS' CONCLUSIONS: The use of early EPO did not significantly reduce the primary outcome of "use of one or more red blood cell transfusions", or "number of transfusions per infant" compared to late EPO administration. Currently there is lack of evidence that early EPO vs. late EPO confers any substantial benefits with regard to any donor blood exposure as a large proportion (14 - 30 %) of infants enrolled in these studies were exposed to donor blood prior to study entry. The finding of a statistically significant increased risk of ROP (any grade) and a similar trend for ROP stage > 3 with early EPO treatment is of great concern. No further studies comparing early vs. late administration of EPO are warranted.

Age Factors↗
PubMed2004

Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients: a systematic review and meta-analysis of randomized trials.

CONTEXT: Neutropenia is one of the grave consequences of cancer chemotherapy, and the treatment of neutropenic febrile patients with intravenous (iv) antibiotics has been shown to reduce mortality. Oral therapy could be an alternative approach for selected patients. OBJECTIVES: To compare the efficacy of oral antibiotics versus iv antibiotic therapy in febrile neutropenic cancer patients. DATA SOURCES: The Cochrane Library, the Cochrane Cancer Network Register of trials, EMBASE, LILACS and MEDLINE, databases for ongoing trials and the conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). STUDY SELECTION: Randomized controlled trials comparing oral antibiotic/s and iv antibiotic/s for the treatment of neutropenic cancer patients with fever. DATA COLLECTION: Two reviewers independently assessed trial eligibility, methodological quality and extracted all data. Data concerning mortality, treatment failures and adverse events were drawn from included studies assuming an 'intention-to-treat' and 'per-protocol' basis for the outcome measures whenever possible. Relative risks (RR) with their 95% confidence intervals (CI) for dichotomous data were estimated. MAIN RESULTS: Fifteen trials (median mortality 0, range 0%-8.8%) were included in the analyses. The mortality rate was similar comparing oral and iv antibiotic treatment (RR 0.83, 95% CI 0.49-1.41, 2224 patients). Treatment failure rates were also similar (RR 0.94, 95% CI 0.84-1.05, 15 trials). No significant heterogeneity was shown for the primary outcomes. This effect was stable in a wide range of patients. Quinolones alone or combined with other antibiotics were used with comparable results. Adverse reactions, mostly gastrointestinal, were more common with oral antibiotics. CONCLUSIONS: Oral antibiotics may be safely offered to neutropenic patients with fever who are at low risk for mortality.

Administration, Oral↗
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↗
PubMed2006

GEDA: new knowledge base of gene expression in drug addiction.

Abuse of drugs can elicit compulsive drug seeking behaviors upon repeated administration, and ultimately leads to the phenomenon of addiction. We developed a procedure for the standardization of microarray gene expression data of rat brain in drug addiction and stored them in a single integrated database system, focusing on more effective data processing and interpretation. Another characteristic of the present database is that it has a systematic flexibility for statistical analysis and linking with other databases. Basically, we adopt an intelligent SQL querying system, as the foundation of our DB, in order to set up an interactive module which can automatically read the raw gene expression data in the standardized format. We maximize the usability of this DB, helping users study significant gene expression and identify biological function of the genes through integrated up-to-date gene information such as GO annotation and metabolic pathway. For collecting the latest information of selected gene from the database, we also set up the local BLAST search engine and nonredundant sequence database updated by NCBI server on a daily basis. We find that the present database is a useful query interface and data-mining tool, specifically for finding out the genes related to drug addiction. We apply this system to the identification and characterization of methamphetamine-induced genes' behavior in rat brain.

Animals↗
PubMed2001

A systematic review of intravesical bacillus Calmette-Guérin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer.

OBJECTIVE: To assess, in a systematic review, the effectiveness of intravesical bacillus Calmette-Guérin (BCG) in preventing tumour recurrence in patients with medium/high risk Ta and T1 bladder cancer. PATIENTS AND METHODS: An electronic database search of Medline, Embase, DARE, the Cochrane Library, Cancerlit, Healthstar and BIDS was undertaken, plus hand searching of the Proceedings of ASCO, for randomized controlled trials, in any language, comparing transurethral resection (TUR) alone with TUR followed by intravesical BCG in patients with Ta and T1 bladder cancer. RESULTS: The search identified 26 publications comparing TUR with TUR + BCG. Six trials were considered acceptable, representing 585 eligible patients, 281 in the TUR-alone group and 304 in the TUR + BCG group. The major clinical outcome chosen was tumour recurrence. The weighted mean log hazard ratio for the first recurrence, taken across all six trials, was -0.83 (95% confidence interval -0.57 to -1.08, P < 0.001), which is equivalent to a 56% reduction in the hazard, attributable to BCG. The Peto odds ratio for patients recurring at 12 months was 0.3 (95% confidence interval of 0.21-0.43, P < 0.001), significantly favouring BCG therapy. Manageable toxicities associated with intravesical BCG were cystitis (67%), haematuria (23%), fever (25%) and urinary frequency (71%). No BCG-induced deaths were reported. CONCLUSION: TUR with intravesical BCG provides a significantly better prophylaxis of tumour recurrence in Ta and T1 bladder cancer than TUR alone. Randomized trials are still needed to address the issues of BCG strain, dose and schedule, and to better quantify the effect on progression to invasive disease.

Administration, Intravesical↗
PubMed2006

Effect of oral decontamination with chlorhexidine on the incidence of nosocomial pneumonia: a meta-analysis.

INTRODUCTION: Nosocomial pneumonia is a significant cause of in-hospital morbidity and mortality. Oral care interventions have great potential to reduce the occurrence of nosocomial pneumonia. Studies using topical antiseptic agents yielded mixed results. We hypothesized that the use of chlorhexidine for oral decontamination would reduce the incidence of nosocomial pneumonia in patients requiring mechanical ventilation. METHODS: This study is a meta-analysis of randomized controlled trials assessing the effect of chlorhexidine on the incidence of nosocomial pneumonia. Data sources were Medline, EMBASE, Cochrane library, citation review of relevant primary and review articles, and contact with expert informants. Out of 1,251 articles screened, 4 randomized, controlled trials were identified that included a total of 1,202 patients. Descriptive and outcome data were extracted by two reviewers independently. Main outcome measures were the incidence of nosocomial pneumonia, and mortality. A random effects model was used. RESULTS: The incidence of nosocomial pneumonia in the control group was 7% (41 out of 615) compared to 4% (24 out of 587) in the treatment group. Gram-negative bacteria accounted for 78% of the total isolates, with Pseudomonas aeruginosa being the most frequently isolated pathogen irrespective of the intervention provided. Duration of mechanical ventilation and intensive care unit length of stay were comparable between the two groups. Overall, the use of oral decontamination with chlorhexidine did not affect the incidence of nosocomial pneumonia (odds ratio of 0.42; 95% confidence interval 0.16-1.06) or the mortality rate (odds ratio 0.77, 95% confidence interval 0.28-2.11). CONCLUSION: The use of oral decontamination with chlorhexidine did not result in significant reduction in the incidence of nosocomial pneumonia in patients who received mechanical ventilation, nor altered the mortality rate. The lack of benefit may reflect the few studies conducted in this area. Future trials should focus on a combination strategy of mechanical and pharmacological interventions.

Administration, Oral↗
PubMed2005

Anabolic steroids for the treatment of weight loss in HIV-infected individuals.

BACKGROUND: Individuals with HIV infection often lose weight during the course of their disease. Furthermore, low serum concentrations of testosterone are common in individuals with HIV infection, particularly those with weight loss. Treatment of weight loss with anabolic steroids in HIV-infected individuals may be beneficial. OBJECTIVES: Our objectives were to assess the efficacy and safety of anabolic steroids for the treatment of weight loss in adults with HIV infection. SEARCH STRATEGY: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, AIDSLINE, AIDSearch, EMBASE, CINAHL, Current Contents, and the National Library of Medicine Gateway Abstracts for controlled trials up to April 2005. We also searched the bibliographies of the identified studies and review the articles. In addition, pharmaceutical manufacturers of anabolic steroids were contacted. SELECTION CRITERIA: Randomized controlled trials that compared the use of an anabolic steroid to placebo to treat weight loss in adults with HIV were included. Randomized controlled trials that compared the use of anabolic steroids to placebo for the treatment of weight loss in adults with HIV were selected. Change from baseline in lean body mass or in body weight was reported as on outcome measure. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trials for quality of randomization, blinding, withdrawals, and adequacy of allocation concealment. For continuous data, weighted mean differences (WMD) were calculated. For dichotomous outcomes, risk differences, were calculated. Because of uncertainty as to whether consistent true effects exist in such different populations and treatments, the authors decided a priori to use random effects models for all outcomes. MAIN RESULTS: Thirteen trials met the inclusion criteria. Two hundred ninety-four individuals randomized to anabolic steroid therapy and 238 individuals randomized to placebo were included in the analysis of efficacy for change from baseline in lean body mass. Three hundred forty-three individuals randomized to anabolic steroid and 286 randomized to placebo were included in the analysis of efficacy for change from baseline in body weight. The mean methodologic quality of the included studies was 4.1, of a maximum 5 points. Although significant heterogeneity was present for both outcomes, the average change in lean body mass was 1.3 kg (95% CI: 0.6, 2.0), while the average change in total body weight was 1.1 kg (95% CI: 0.3, 2.0). A total of eight deaths occurred during the treatment period; four in the anabolic steroid treatment groups and four in the placebo-treatment groups (risk difference 0.00, 95% CI -0.03, 0.03). The risk difference for withdrawals or discontinuations of study medication due to adverse events was 0.00 (95% CI: -0.02, 0.03). AUTHORS' CONCLUSIONS: Although the results of the trials were heterogeneous, on average, the administration of anabolic steroids appeared to result in a small increase in both lean body mass and body weight as compared with placebo. While these results suggest that anabolic steroids may be useful in the treatment of weight loss in HIV infected individuals, due to limitations, treatment recommendations cannot be made. Further information is required regarding the long-term benefit and adverse effects of anabolic steroid use, the specific populations for which anabolic steroid therapy may be most beneficial, and the optimal regime. In addition, the correlation of improvement in lean body mass with more clinically relevant endpoints, such as physical functioning and survival, needs to be determined.

Anabolic Agents↗
PubMed2004

Cranberries for preventing urinary tract infections.

BACKGROUND: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in preventing such infections. OBJECTIVES: To assess the effectiveness of cranberry juice and other cranberry products in preventing UTIs in susceptible populations. SEARCH STRATEGY: Electronic databases and the Internet were searched using English and non English language terms; companies involved with the promotion and distribution of cranberry preparations were contacted; reference lists of review articles and relevant trials were searched. Cochrane Central Register of Controlled Trials (CENTRAL - the Cochrane Library, issue 1, 2003) was searched in February 2003. SELECTION CRITERIA: All randomised or quasi randomised controlled trials of cranberry juice/products for the prevention of urinary tract infections in susceptible populations. Trials of men, women or children were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (urinary tract infections (symptomatic and asymptomatic), side effects and adherence to therapy). RR were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane criteria. MAIN RESULTS: Seven trials met the inclusion criteria (four cross-over, three parallel group). The effectiveness of cranberry juice (or cranberry-lingonberry juice) versus placebo juice or water was evaluated in six trials, and the effectiveness of cranberries tablets versus placebo was evaluated in two trials (one study evaluated both juice and tablets). In two good quality RCTs, cranberry products significantly reduced the incidence of UTIs at twelve months (RR 0.61 95% CI:0.40 to 0.91) compared with placebo/control in women. One trial gave 7.5 g cranberry concentrate daily (in 50 ml), the other gave 1:30 concentrate given either in 250 ml juice or in tablet form. There was no significant difference in the incidence of UTIs between cranberry juice versus cranberry capsules (RR 1.11 95% CI:0.49 to 2.50). Five trials were not included in the meta-analyses due to methodological flaws or lack of available data. However, only one reported a significant result for the outcome of symptomatic UTIs. Side effects were common in all trials, and dropouts/withdrawals in several of the trials were high. REVIEWERS' CONCLUSIONS: There is some evidence from two good quality RCTs that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period in women. If it is effective for other groups such as children and elderly men and women is not clear. The large number of dropouts/withdrawals from some of the trials indicates that cranberry juice may not be acceptable over long periods of time. In addition it is not clear what is the optimum dosage or method of administration (e.g. juice or tablets). Further properly designed trials with relevant outcomes are needed.

Beverages↗
PubMed2005

Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis.

BACKGROUND: Vitamin D and related compounds have been used to prevent fractures. OBJECTIVES: To determine the effects of vitamin D or analogues, with or without calcium, in the prevention of fractures in older people. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group trials register, the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE, EMBASE, CINAHL, and reference lists of articles. Most recent search: March 2005. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing vitamin D or an analogue, alone or with calcium, against placebo, no intervention, or calcium, reporting fracture outcomes, in older people. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality, and extracted data. Data were pooled, where admissible, using the fixed-effect model, or random-effects model if the relative risks were heterogeneous. MAIN RESULTS: Vitamin D alone showed no statistically significant effect on hip fracture (seven trials, 18,668 participants, RR 1.17, 95% CI 0.98 to 1.41), vertebral fracture (four trials, 5698 participants, RR (random effects) 1.13, 95% CI 0.50 to 2.55) or any new fracture (eight trials, 18,903 participants, RR 0.99, 95% CI 0.91 to 1.09). Vitamin D with calcium marginally reduced hip fractures (seven trials, 10,376 participants, RR 0.81, 95% CI 0.68 to 0.96), non-vertebral fractures (seven trials, 10,376 participants, RR 0.87, 95% CI 0.78 to 0.97), but there was no evidence of effect of vitamin D with calcium on vertebral fractures. The effect appeared to be restricted to those living in institutional care. Hypercalcaemia was more common when vitamin D or its analogues was given compared with placebo or calcium (14 trials, 8035 participants, RR 2.38, 95% CI 1.52 to 3.71). The risk was particularly high with calcitriol (three trials, 742 participants, RR 14.94, 95% CI 2.95 to 75.61). There was no evidence that vitamin D increased gastro-intestinal symptoms (seven trials, 10,188 participants, RR (random effects) 1.03, 95% CI 0.79 to 1.36) or renal disease (nine trials, 10,107 participants, RR 0.80, 95% CI 0.34 to 1.87). AUTHORS' CONCLUSIONS: Frail older people confined to institutions may sustain fewer hip and other non-vertebral fractures if given vitamin D with calcium supplements. Effectiveness of vitamin D alone in fracture prevention is unclear. There is no evidence of advantage of analogues of vitamin D compared with vitamin D. Calcitriol may be associated with an increased incidence of adverse effects. Dose, frequency, and route of administration of vitamin D in older people require further investigation.

Aged↗
PubMed2004

Cranberries for preventing urinary tract infections.

BACKGROUND: Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections (UTIs). The aim of this review is to assess the effectiveness of cranberries in preventing such infections. OBJECTIVES: To assess the effectiveness of cranberry juice and other cranberry products in preventing UTIs in susceptible populations. SEARCH STRATEGY: Electronic databases and the Internet were searched using English and non English language terms; companies involved with the promotion and distribution of cranberry preparations were contacted; reference lists of review articles and relevant trials were searched. Cochrane Central Register of Controlled Trials (CENTRAL - the Cochrane Library, issue 1, 2003) was searched in February 2003. SELECTION CRITERIA: All randomised or quasi randomised controlled trials of cranberry juice/products for the prevention of urinary tract infections in susceptible populations. Trials of men, women or children were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted information. Information was collected on methods, participants, interventions and outcomes (urinary tract infections (symptomatic and asymptomatic), side effects and adherence to therapy). RR were calculated where appropriate, otherwise a narrative synthesis was undertaken. Quality was assessed using the Cochrane criteria. MAIN RESULTS: Seven trials met the inclusion criteria (four cross-over, three parallel group). The effectiveness of cranberry juice (or cranberry-lingonberry juice) versus placebo juice or water was evaluated in six trials, and the effectiveness of cranberries tablets versus placebo was evaluated in two trials (one study evaluated both juice and tablets). In two good quality RCTs, cranberry products significantly reduced the incidence of UTIs at twelve months (RR 0.61 95% CI:0.40 to 0.91) compared with placebo/control in women. One trial gave 7.5 g cranberry concentrate daily (in 50 ml), the other gave 1:30 concentrate given either in 250 ml juice or in tablet form. There was no significant difference in the incidence of UTIs between cranberry juice versus cranberry capsules (RR 1.11 95% CI:0.49 to 2.50). Five trials were not included in the meta-analyses due to methodological flaws or lack of available data. However, only one reported a significant result for the outcome of symptomatic UTIs. Side effects were common in all trials, and dropouts/withdrawals in several of the trials were high. REVIEWER'S CONCLUSIONS: There is some evidence from two good quality RCTs that cranberry juice may decrease the number of symptomatic UTIs over a 12 month period in women. If it is effective for other groups such as children and elderly men and women is not clear. The large number of dropouts/withdrawals from some of the trials indicates that cranberry juice may not be acceptable over long periods of time. In addition it is not clear what is the optimum dosage or method of administration (e.g. juice or tablets). Further properly designed trials with relevant outcomes are needed.

Beverages↗
PubMed2005

Three-day vs longer duration of antibiotic treatment for cystitis in women: systematic review and meta-analysis.

PURPOSE: We performed a meta-analysis to ascertain the efficacy and safety of the currently practiced 3-day antibiotic therapy for cystitis versus prolonged therapy (5 days or longer) to relieve symptoms and to achieve bacteriological cure. METHODS: The Cochrane Library, the Cochrane Renal Group's Register of trials, EMBASE and MEDLINE were searched to identify all randomized controlled trials comparing 3-day oral antibiotic therapy with prolonged therapy (5 days and longer) for uncomplicated cystitis in adult non-pregnant women. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. Relative risks (RR) with their 95% confidence intervals (CI) were estimated; a fixed effect model was used. An intention-to-treat analysis was performed whenever possible. RESULTS: Thirty-two trials and 9605 patients met inclusion criteria. For symptomatic failure rates no difference between 3-day and prolonged antibiotic regimens was found at short term (RR 1.16, 95% CI: 0.96-1.41) and long-term follow-up (RR 1.17, 95% CI: 0.99-1.38). Three-day treatment was less effective than prolonged therapy in preventing bacteriological failure, relative risk 1.37 (95% CI: 1.07-1.74) for short-term follow-up, and 1.47 (95% CI: 1.22-1.77) for long-term follow-up. Adverse effects were more common in the prolonged therapy group (RR 0.83, 95% CI: 0.79-0.91). The results were consistent for subgroup and sensitivity analyses. CONCLUSION: Antibiotic therapy for 3 days is similar to prolonged therapy in achieving symptomatic cure for cystitis, while the prolonged treatment is more effective in obtaining bacteriological cure.

Administration, Oral↗
PubMed1999

A new CYP2A6 gene deletion responsible for the in vivo polymorphic metabolism of (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride in humans.

(+)-Cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) is a newly developed drug as a platelet-activating factor receptor antagonist. The disposition of SM-12502 was investigated in plasma from 28 healthy Japanese volunteers after a single i.v. administration of SM-12502. Three of 28 subjects were phenotyped as poor metabolizers (PMs). Genomic DNAs from three extensive metabolizers or three PMs of SM-12502 were analyzed by Southern blot analysis with CYP2A6 cDNA as a probe. DNAs from three PMs digested with SacI and SphI showed novel restriction fragment length polymorphisms (RFLPs); one type without 4.5- and 2.6-kb fragments and a weak density of a 6.4-kb fragment (E-type), and the other type without 7.1- and 5.5-kb restriction fragments (C'-type) as compared with three extensive metabolizers, respectively. The deletional restriction fragments specific to three PMs in SacI- and SphI-RFLPs were identified as CYP2A6. Using polymerase chain reaction-RFLP analyses of the gene from the three PMs, we found that the exon 1, exon 8, and exon 9 in CYP2A6 were absent. A new RFLP characterized by SacI and SphI was found to be due to the entire gene deletion of the three exons and was associated with the decreased metabolism of SM-12502. This study demonstrates a new deletional allele in the human CYP2A6 gene responsible for the poor metabolic phenotype of SM-12502.

Adult↗
PubMed2002

[Orofacial herpes and other localizations (genital herpes and neonatal herpes excluded)].

BACKGROUND: Herpes is a pandemic infection in the human species. The purpose of this work was to conduct a critical analysis of the literature devoted to the pathophysiology and treatment of orofacial herpes an other localizations (genital herpes and neonatal herpes excluded). METHODS: We searched for articles in English and French devoted to orofacial herpes and other herpetic localizations indexed in Medline (1980-July 001), EmBase, and the Cochrane Library (1995-July 2001). Critical analysis was based on level of proof using the ANAES methodology. RESULTS: More than 700 articles were identified. One hundred four were selected for this report. Primary HSV1 infection usually occurred before adulthood and involved acute gingivo-stomatitis in the majority of the cases. Several primary HIV1 infections were asymptomatic or aspecific and non-recognized. After the primary infection, the virus remains in the ganglion of the trigeminal nerve in a latent state and can be reactivated sporadically. Reactivation is associated with viral excretion and can be symptomatic (herpetic recrudescence) or not (recurrence). Recrudescence of orofacial herpes is typically labial. No currently available vaccine can prevent acquisition of HSV1. Treatment of acute gingivostomatitis has been standardized and is based on aciclovir. Inversely, the effectiveness of aciclovir and other nucleoside analogs with anti-herpes activity has not been clearly established for prevention or cure of recrudescence of orofacial herpes. Other localizations (hand, anus, diffuse skin localizations in contact sports, Kaposi-Juliusberg syndrome) are much more exceptional. Treatment has not been standardized. DISCUSSION: Despite the abundance of the literature on orofacial herpes, consistent quality is lacking, particularly concerning therapeutic studies. The quality of these reports is generally inferior to those devoted to genital herpes. There has however been a general trend towards improved methodology over the last years. Very little has been reported on exceptional localizations of orofacial herpes.

Acyclovir↗