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PubMed2004

Amantadine and rimantadine for preventing and treating influenza A in adults.

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but these drugs are not widely used due to a lack of knowledge of their potential value and concerns about possible adverse effects. OBJECTIVES: The objective of this review was to assess the effectiveness and safety ("effects") of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003), MEDLINE (January 1966 to November week 2, 2003), EMBASE (January 1990 to September 2003) and the reference lists of articles. We also contacted manufacturers, researchers and authors. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prevention trials the numbers of participants with clinical influenza (influenza-like-illness or ILI), i.e. confirmed influenza A, and adverse effects were analysed. Analysis for treatment trials included the mean duration of fever and length of hospital stay, and the number of adverse effects. MAIN RESULTS: Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of fever by one day (95% CI 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system and study withdrawals were significantly more common with amantadine than rimantadine. REVIEWERS' CONCLUSIONS: Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine causes fewer adverse effects than amantadine.

Adult↗

PubMed2002

Non-steroidal anti-inflammatory drugs (NSAIDs) for treating lateral elbow pain in adults.

BACKGROUND: Lateral elbow pain, or tennis elbow, is a common condition causing pain in the elbow and forearm and lack of strength and function of the elbow and wrist. It is often treated with non-steroidal anti-inflammatory drugs (NSAIDs), either orally or by topical application. OBJECTIVES: To assess effectiveness of NSAIDs (oral or topical) in the treatment of adults with lateral elbow pain with respect to symptom (pain) reduction, improvement in function, grip strength and adverse effects. SEARCH STRATEGY: We searched the Musculoskeletal Review Group's trials register database, the Cochrane Clinical Trials Register (Cochrane Library issue 2, 2001), MEDLINE, CINAHL, EMBASE and SCISEARCH up to June 2001. SELECTION CRITERIA: Randomised and pseudo randomised trials in all languages of NSAIDs (oral or topical) compared to placebo or another intervention, or comparing two NSAIDs (oral or topical) to each other, in adults with lateral elbow pain (tennis elbow). Outcomes of interest were pain, function, disability and quality of life, strength, participant satisfaction with treatment and adverse effect. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied selection criteria and assessed study quality. MAIN RESULTS: Fourteen trials were included in the review. Few trials used intention to treat analysis, and the sample size of most was small. The median follow up was 2 weeks (range 1-12 weeks). There is evidence that topical NSAIDs are significantly more effective than placebo with respect to pain [weighted main difference= -1.88, (95% confidence intervals -2.54 to -1.21)] and participant satisfaction [relative risk 0.39, (95% confidence intervals 0.23 to 0.66)] in the short term, and this finding is robust against the possible bias introduced by the inclusion of unblinded trials and publication bias. The adverse effects reported were minor. Only two included trials assessed the effect of oral NSAID and these were not able to be pooled. There is some evidence for short term benefit with respect to pain and function from oral NSAIDs, but this benefit was not sustained. Significantly more gastrointestinal adverse effects were reported by those taking oral NSAIDs [relative risk = 3.17, (95% confidence intervals 1.35 to 7.41)]. In the short term there may be some advantage in steroid injection over oral NSAID [patient's perception of benefit relative risk = 3.06, (95% confidence intervals 1.55 to 6.06)], but this was not sustained in the longer term. REVIEWER'S CONCLUSIONS: There is some support for the use of topical NSAIDs to relieve lateral elbow pain at least in the short term. There remains insufficient evidence to recommend or discourage the use of oral NSAID, although it appears injection may be more effective than oral NSAID in the short term. A direct comparison between topical and oral NSAID has not been made and so no conclusions can be drawn regarding the best method of administration.

Administration, Oral↗

PubMed2004

Additional bedtime H2-receptor antagonist for the control of nocturnal gastric acid breakthrough.

BACKGROUND: Nocturnal gastric acid breakthrough(NAB) is defined as intragastric pH<4 for more than one continuous hour overnight. Adding H2-receptor antagonists (H2RAs)at bedtime to high-dose proton pump inhibitors is likely to enhance nocturnal gastric pH control and decrease nocturnal gastric acid breakthrough. OBJECTIVES: To assess the effectiveness of additional bedtime H2-receptor antagonists in suppressing nocturnal gastric acid breakthrough and the incidence of adverse effects. SEARCH STRATEGY: We identified eligible trials by searching The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003), MEDLINE (1966-July 2003), EMBASE (1980-July 2003) and CINAHL (1982-July 2003). We re-ran the search on CENTRAL (The Cochrane Library Issue 2, 2004), and in MEDLINE, EMBASE and CINAHL in June 2004. SELECTION CRITERIA: All randomized controlled trials evaluating H2-receptor antagonists for the control of nocturnal gastric acid breakthrough were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We extracted data and recorded relevant information onto specially developed forms. One reviewer extracted data and a second reviewer checked data extraction. We have also double-checked data entry into RevMan. For binary outcomes, we expressed the impact of the intervention as relative risks, together with 95% confidence intervals. For scale-based outcomes, we used means and standard deviations to summarise the values in each group, provided the scale permitted sufficient values. We had intended to analyse such outcomes for the presence of skew, but the studies included were too limited to permit this. MAIN RESULTS: Two randomized crossover studies including 32 participants met the inclusion criteria. Because the design, dosage and duration of the treatment were different between the studies, it was not possible to conduct meta-analysis. There is no consistent conclusion between the two included studies in evaluating H2RAs for the control of NAB. REVIEWERS' CONCLUSIONS: We can conclude no implications for practice at this stage. Appropriately designed, large-scale randomized controlled trials with long-term follow-up are needed to determine the effects of additional bedtime H2RAs in suppressing nocturnal gastric acid breakthrough.

Drug Administration Schedule↗

PubMed2002

[Tropisetron for prevention of postoperative nausea and vomiting: a quantitative systematic review].

OBJECTIVE: A quantitative systematic review of randomised controlled trials investigating the efficacy of tropisetron versus placebo to prevent postoperative nausea (PN) and vomiting (PV) as well as PN and/or PV (PONV). METHODS: The relevant results for the 24 h postoperative period were extracted from systematically searched studies (MEDLINE, EMBASE, Cochrane-Library, reference lists; last update December 2001). RESULTS: In 19 studies and 22 comparisons, 1,012 patients received a placebo and 1,267 patients tropisetron and the pooled analyses (2-5 mg iv) are presented. The relative risks (RR) for PN, PV and PONV with tropisetron prophylaxis were 0.72 (95%-CI: 0.62-0.83), 0.59 (95%-CI: 0.47-0.73) and 0.70 (95%-CI: 0.62-0.79), respectively. The RR for rescue treatment was 0.63 (95%-CI: 0.54-0.74). The RR in children for a variable dose of 0.1-0.2 mgxkg(-1) was 0.49 (95%-CI: 0.38-0.63), 0.49 (95%-CI: 0.38-0.63) and 0.32 (95%-CI: 0.15-0.70) for PV, PONV and rescue treatment, respectively. Restricting the analysis to a predefined control event rate of 40-80% revealed that about 6-7 patients need to be treated with tropisetron for PN to be prevented in 1 patient who would have had PN if all had received a placebo (NNT=6.7; 95%-CI: 4.8-11.1). The corresponding NNT for preventing PV and PONV was 5.0 (95%-CI: 3.6-8.3) and 4.6 (95%-CI: 3.6-6.3), respectively. CONCLUSION: Tropisetron significantly reduced the incidence of PONV. There is no clear evidence for a dose response between 2 and 5 mg iv. For children a dose of 0.1 mgxkg(-1) of body weight is effective. Sufficient data for the oral application of tropisetron are lacking.

Administration, Oral↗

PubMed2026

Reassessment of the effect of oral l-arginine on blood pressure: A systematic review and meta-analysis based on ambulatory blood pressure monitoring.

OBJECTIVE: This meta-analysis aimed to evaluate the effect of oral l-arginine supplementation on ambulatory blood pressure (ABP). METHODS: A systematic search of PubMed, Cochrane Library, Embase, and Web of Science databases was conducted from their inception through March 1, 2026. Randomized controlled trials (RCTs) assessing the effects of oral l-arginine intervention were included. Outcome measures included 24-h systolic blood pressure (24h SBP), 24-h diastolic blood pressure (24h DBP), daytime systolic blood pressure (dSBP), daytime diastolic blood pressure (dDBP), nighttime systolic blood pressure (nSBP), and nighttime diastolic blood pressure (nDBP). Meta-analysis was performed using Stata 17.0. The weighted mean difference (WMD) was used as the effect size, and the results were pooled with 95% confidence intervals (CIs). RESULTS: A total of 5 RCTs comprising 202 participants were included. Meta-analysis results demonstrated that oral l-arginine significantly reduced 24h SBP (WMD = -4.23 mmHg, 95% CI [-5.87, -2.58]; P < 0.01) and 24h DBP (WMD = -3.04 mmHg, 95% CI [-4.48, -1.59]; P < 0.01). Significant reductions were also observed for dSBP (WMD = -4.16 mmHg, 95% CI [-5.90, -2.41]; P < 0.01) and dDBP (WMD = -4.25 mmHg, 95% CI [-5.85, -2.66]; P < 0.01). Furthermore, oral l-arginine significantly lowered nSBP (WMD = -5.70 mmHg, 95% CI [-7.81, -3.58]; P < 0.01) and nDBP (WMD = -4.18 mmHg, 95% CI [-6.27, -2.09]; P < 0.01). CONCLUSION: Oral l-arginine supplementation significantly reduces ABP. However, the number of included studies was limited, and further validation through additional relevant research is warranted.

Arginine↗

PubMed2004

Hypnosis for pain relief in labour and childbirth: a systematic review.

BACKGROUND: In view of widespread claims of efficacy, we examined the evidence regarding the effects of hypnosis for pain relief during childbirth. METHODS: Medline, Embase, Pubmed, and the Cochrane library 2004.1 were searched for clinical trials where hypnosis during pregnancy and childbirth was compared with a non-hypnosis intervention, no treatment or placebo. Reference lists from retrieved papers and hypnotherapy texts were also examined. There were no language restrictions. Our primary outcome measures were labour analgesia requirements (no analgesia, opiate, or epidural use), and pain scores in labour. Suitable comparative studies were included for further assessment according to predefined criteria. Meta-analyses were performed of the included randomized controlled trials (RCTs), assessed as being of "good" or "adequate" quality by a predefined score. RESULTS: Five RCTs and 14 non-randomized comparisons (NRCs) studying 8395 women were identified where hypnosis was used for labour analgesia. Four RCTs including 224 patients examined the primary outcomes of interest. One RCT rated poor on quality assessment. Meta-analyses of the three remaining RCTs showed that, compared with controls, fewer parturients having hypnosis required analgesia, relative risk=0.51 (95% confidence interval 0.28, 0.95). Of the two included NRCs, one showed that women using hypnosis rated their labour pain less severe than controls (P<0.01). The other showed that hypnosis reduced opioid (meperidine) requirements (P<0.001), and increased the incidence of not requiring pharmacological analgesia in labour (P<0.001). CONCLUSION: The risk/benefit profile of hypnosis demonstrates a need for well-designed trials to confirm the effects of hypnosis in childbirth.

Analgesia, Obstetrical↗

PubMed2005

Phosphodiesterase III inhibitors for heart failure.

BACKGROUND: In the treatment of chronic heart failure, vasodilating agents, ACE inhibitors and beta-blockers have shown an increase of life expectancy. Another strategy is to increase the inotropic state of the myocardium : phosphodiesterase inhibitors (PDIs) act by increasing intra-cellular cyclic AMP, thereby increasing the concentration of intracellular calcium, and lead to a positive inotropic effect. OBJECTIVES: This overview on summarised data aims to review the data from all randomised controlled trials of PDIs III versus placebo in symptomatic patients with chronic heart failure. The primary endpoint is total mortality. Secondary endpoints are considered such as cause-specific mortality, worsening of heart failure (requiring intervention), myocardial infarction, arrhythmias and vertigos. We also examine whether the therapeutic effect is consistent in the subgroups based on the use of concomitant vasodilators, the severity of heart failure, and the type of PDI derivative and/or molecule. This overview updates our previous meta-analysis published in 1994. SEARCH STRATEGY: Randomised trials of PDIs versus placebo in heart failure were searched using MEDLINE (1966 to 2004 January), EMBASE (1980 to 2003 December), Cochrane CENTRAL trials (The Cochrane Library Issue 1, 2004) and McMaster CVD trials registries, and through an exhaustive handsearching of international abstracting publications (abstracts published in the last 22 years in the "European Heart Journal", the "Journal of the American College of Cardiology" and "Circulation"). SELECTION CRITERIA: All randomised controlled trials of PDIs versus placebo with a follow-up duration of more than three months. DATA COLLECTION AND ANALYSIS: 21 trials (8408 patients) were eligible for inclusion in the review. 4 specific PDI derivatives and 8 molecules of PDIs have been considered. MAIN RESULTS: As compared with placebo, treatment with PDIs was found to be associated with a significant 17% increased mortality rate (The relative risk was 1.17 (95% confidence interval 1.06 to 1.30; p<0.001). In addition, PDIs significantly increase cardiac death, sudden death, arrhythmias and vertigos. Considering mortality from all causes, the deleterious effect of PDIs appears homogeneous whatever the concomitant use (or non-use) of vasodilating agents, the severity of heart failure, the derivative or the molecule of PDI used. AUTHORS' CONCLUSIONS: Our results confirm that PDIs are responsible for an increase in mortality rate compared with placebo in patients suffering from chronic heart failure. Currently available results do not support the hypothesis that the increased mortality rate is due to additional vasodilator treatment. Consequently, the chronic use of PDIs should be avoided in heart failure patients.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMedDate not supplied

Efficacy and safety of inhaled corticosteroids in patients with COPD: a systematic review and meta-analysis of health outcomes.

PURPOSE: We wanted to review systematically the efficacy, effectiveness, and safety of inhaled corticosteroids with respect to health outcomes in patients with chronic obstructive pulmonary disease (COPD). METHODS: We searched MEDLINE, EMBASE, The Cochrane Library, and the International Pharmaceutical Abstracts to identify relevant articles. We limited evidence to double-blinded randomized controlled trials (RCTs) for efficacy, but we also reviewed observational evidence for safety. Outcomes of interest were overall mortality, exacerbations, quality of life, functional capacity, and respiratory tract symptoms. When possible, we pooled data to estimate summary effects for each outcome. RESULTS: Thirteen double-blinded RCTs determined the efficacy of an inhaled corticosteroid compared with placebo; 11 additional studies assessed the safety of inhaled corticosteroid treatment in patients with asthma or COPD. Overall, COPD patients treated with inhaled corticosteroids experienced significantly fewer exacerbations than patients taking placebo (relative risk [RR] = 0.67; 95% CI, 0.59-0.77). No significant difference could be detected for overall mortality (RR = 0.81; 95% CI, 0.60-1.08). Evidence on quality of life, functional capacity, and respiratory tract symptoms is mixed. Adverse events were generally tolerable; pooled discontinuation rates did not differ significantly between inhaled corticosteroid and placebo treatment groups (RR = 0.92; 95% CI, 0.74-1.14). Observational evidence, however, indicates a dose-related risk of cataract and open-angle glaucoma. Severe adverse events, such as osteoporotic fractures, are rare; the clinical importance of the additional risk is questionable. CONCLUSIONS: Overall, the risk-benefit ratio appears to favor inhaled corticosteroid treatment in patients with moderate to severe COPD. Existing evidence does not indicate a treatment benefit for patients with mild COPD.

Administration, Inhalation↗

PubMed2005

Ximelagatran: a new type of oral anticoagulant.

OBJECTIVES: This assessment sought to evaluate the comparative benefit and adverse effect profile of ximelagatran, as well as the clinical issues surrounding its potential use. METHODS: We performed a Dialog OneSearch across BIOSIS Previews, EMBASE, MEDLINE, PASCAL, and ToxFile to identify published literature. PubMed and The Cochrane Library were also searched. Gray literature was identified by searching a variety of Web sites of health technology assessment and related agencies and their associated databases. The manufacturer's Canadian office, AstraZeneca, was invited to submit information. RESULTS: Ximelagatran is the first oral agent from a new class of anticoagulants called direct thrombin inhibitors. Other oral anticoagulants require routine blood monitoring; ximelagatran does not. Ximelagatran has been evaluated in the areas of venous thromboembolism management, particularly after orthopedic surgery, and stroke prevention in patients with atrial fibrillation. Overall, ximelagatran's efficacy appears comparable to other anticoagulants in these clinical settings. Also, bleeding rates were generally similar between ximelagatran and comparators but, as for warfarin, bleeding risk increases with higher ximelagatran doses. In addition, there is no specific antidote to help manage ximelagatran-induced bleeding. Finally, significantly more patients exposed to long-term ximelagatran developed elevated liver enzymes more than three times the upper normal limit, compared with patients on comparator anticoagulants. CONCLUSIONS: Given its apparent simplicity of use, ximelagatran carries the potential to replace, at least in part, anticoagulants currently used in the management of venous thromboembolism or for preventing stroke in atrial fibrillation patients. However, the safety of ximelagatran will not be fully known without further evaluation and surveillance for potential liver toxicity. There is also a need to evaluate its use in special populations such as patients with renal failure and patients using several concurrent medications.

Administration, Oral↗

PubMed2004

Systematic review of topical capsaicin for the treatment of chronic pain.

OBJECTIVE: To determine the efficacy and safety of topically applied capsaicin for chronic pain from neuropathic or musculoskeletal disorders. DATA SOURCES: Cochrane Library, Medline, Embase, PubMed, an in-house database, and contact with manufacturers of topical capsaicin. STUDY SELECTION: Randomised controlled trials comparing topically applied capsaicin with placebo or another treatment in adults with chronic pain. DATA EXTRACTION: Primary outcome was dichotomous information for the number of patients with about a 50% reduction in pain. Outcomes were extracted at four weeks for musculoskeletal conditions and eight weeks for neuropathic conditions. Secondary outcomes were adverse events and withdrawals due to adverse events. DATA SYNTHESIS: Six double blind placebo controlled trials (656 patients) were pooled for analysis of neuropathic conditions. The relative benefit from topical capsaicin 0.075% compared with placebo was 1.4 (95% confidence interval 1.2 to 1.7) and the number needed to treat was 5.7 (4.0 to 10.0). Three double blind placebo controlled trials (368 patients) were pooled for analysis of musculoskeletal conditions. The relative benefit from topical capsaicin 0.025% or plaster compared with placebo was 1.5 (1.1 to 2.0) and the number needed to treat was 8.1 (4.6 to 34). Around one third of patients experienced local adverse events with capsaicin, which would not have been the case with placebo. CONCLUSIONS: Although topically applied capsaicin has moderate to poor efficacy in the treatment of chronic musculoskeletal or neuropathic pain, it may be useful as an adjunct or sole therapy for a small number of patients who are unresponsive to, or intolerant of, other treatments.

Administration, Topical↗

PubMed2005

Inhaled nitric oxide for the postoperative management of pulmonary hypertension in infants and children with congenital heart disease.

BACKGROUND: Nitric oxide (NO) is a prevalent molecule in the human body responsible for many physiologic activities including pulmonary vasodilation. An exogenous, inhaled form (iNO) exists that mimics this action without directly affecting systemic blood pressure. This therapy has been implemented in the treatment of pulmonary hypertension. This review examines the efficacy of iNO in the postoperative management of infants and children with congenital heart disease. OBJECTIVES: To compare the effects of postoperative iNO versus placebo and/or conventional management on infants and children with congenital heart disease. The primary outcome was mortality, while secondary outcomes included length of hospital stay, assessment of neurodevelopmental disability, number of pulmonary hypertensive crises (PHTC), changes in haemodynamics including mean pulmonary arterial pressure (MPAP), mean arterial pressure (MAP), and heart rate (HR), changes in oxygenation measured as the ratio PaO2:FiO2, and measurement of maximum methaemoglobin level as a marker of toxicity. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2004), MEDLINE (1966 to 2004), and EMBASE (1980 to 2004). We included abstracts and all languages. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing iNO with placebo and conventional management, or both. Trials included only children with congenital heart disease requiring surgery and complicated by pulmonary hypertension. DATA COLLECTION AND ANALYSIS: Data were collected on mortality, number of PHTC, changes in MPAP, MAP, HR, and PaO2:FiO2, and maximum methaemoglobin level, while data on long-term mortality, neurodevelopmental disability, and length of hospital stay were unavailable. We performed subgroup analysis by age and method of control. We performed sensitivity analysis using studies of highest methodologic quality. MAIN RESULTS: We included four randomized trials. We observed no differences between groups with respect to mortality (P = 0.50), PHTC (P = 0.79), change in MPAP (P = 0.16), MAP (P = 0.40), HR (P = 1.00), or PaO2:FiO2 (P = 0.46). There was a significant reduction in MPAP in the subgroup of patients from birth to three months (P = 0.005), although this finding was based on a small number of patients (N = 23). AUTHORS' CONCLUSIONS: We observed no differences with the use of iNO as compared with control in the majority of outcomes reviewed. No data were available for analysis with respect to several clinical outcomes including long-term mortality and neurodevelopmental outcome. We found it difficult to draw valid conclusions because of concerns regarding methodologic quality, bias, sample size, and heterogeneity.

Administration, Inhalation↗

PubMed2000

Oral vasoactive medication in intermittent claudication: utile or futile?

OBJECTIVE: To evaluate the role of orally administered vasoactive medication in the management of intermittent claudication. SETTING: We limited our study to the products on the market in Belgium: cinnarizine, cyclandelate, isoxsuprine, naftidrofuryl, pentoxifylline, xanthinol nicotinate and buflomedil. DATA SOURCES: We conducted a systematic literature search involving Medline, International Pharmaceutical Abstracts, the Cochrane Library, direct contact with marketing companies and key authors, snowballing and Science Citation Index search. We looked for randomised placebo-controlled trials (RCTs) in patients with Fontaine stage II, in which pain-free and/or maximal walking distance were measured using a standardised exercise test. For isoxsuprine and xanthinol nicotinate, no trials conforming to these criteria were found. Thirty-six trials on cinnarizine, cyclandelate, buflomedil, naftidrofuryl and pentoxifylline met our inclusion criteria. STUDY SELECTION: After quality assessment, 26 trials were excluded, mainly because of short trial duration (less than 12 weeks), small sample size (less than 30 patients) and/or failure to report details on variability (standard deviation or confidence limits). For cinnarizine and cyclandelate, none of the three selected RCTs was included. DATA EXTRACTION: For buflomedil, of six published RCTs, two were included after quality assessment, each showing a marginally positive effect of buflomedil versus placebo. For naftidrofuryl, nine RCTs were selected; six were included of which five showed a significant positive result. The likelihood of publication bias and the heterogeneity of the results within and between trials precluded a meta-analysis. For pentoxifylline, of the 18 selected RCTs, only two could be included, both with inconclusive results. CONCLUSION: A national consensus conference, based on this review, concluded that health resources should be allocated to prevention and rehabilitation of intermittent claudication rather than to reimbursement of these products with doubtful efficacy.

Administration, Oral↗

PubMed2003

Intramuscular penicillin is more effective than oral penicillin in secondary prevention of rheumatic fever--a systematic review.

BACKGROUND: People with a history of rheumatic fever (RF) are at high risk of recurrent attacks and of developing rheumatic heart disease following a streptococcal throat infection. Giving penicillin to these people can prevent recurrent attacks of RF and subsequent rheumatic heart disease. However, there is no agreement on the most effective method of giving penicillin. OBJECTIVES: To assess the effects of different penicillin regimens and formulations for preventing streptococcal infection and RF recurrence. SEARCH STRATEGY: We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), Medline (January 1966-July 2000), Embase (January 1985-July 2000), reference lists of articles, and contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing: (i) oral with intramuscular penicillin; and (ii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous RF. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Six studies were included (1,707 patients). Data were not pooled because of clinical and methodological heterogeneity of the trials. Four trials (1,098 patients) compared intramuscular with oral penicillin and all showed that intramuscular penicillin was more effective in reducing RF recurrence and streptococcal throat infections than oral penicillin. One trial (360 patients) compared 2-weekly with 4-weekly intramuscular penicillin. Penicillin given every 2 weeks was better at reducing RF recurrence (relative risk (RR) 0.52, 95% confidence interval (CI): 0.33-0.83) and streptococcal throat infections (RR 0.60, 95% CI: 0.42-0.85). One trial (249 patients) showed that 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI: 0.48-0.92) compared with 4-weekly intramuscular penicillin. CONCLUSIONS: Intramuscular penicillin seemed to be more effective than oral penicillin in preventing RF recurrence and streptococcal throat infections. Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections. However, the evidence is based on poor-quality trials and the use of outdated formulations of oral penicillin.

Administration, Oral↗

PubMed2005

Short-course therapy with rifampin plus isoniazid, compared with standard therapy with isoniazid, for latent tuberculosis infection: a meta-analysis.

BACKGROUND: A major difficulty associated with the use of standard therapy with isoniazid for latent tuberculosis infection is poor patient adherence to therapy because of the prolonged course required. Shorter courses of therapy involving > or =2 drugs have been proposed as an alternative to standard therapy, but they have not undergone enough testing. METHODS: We performed a meta-analysis to determine the equivalence of daily short-course therapy with rifampin plus isoniazid for 3 months and standard therapy with isoniazid for 6-12 months. The end points that were evaluated were development of active tuberculosis, severe adverse drug reactions, and death. We searched published information in the Cochrane Library, MEDLINE, and Embase databases, as well as unpublished information in the Cambridge Scientific Abstracts Internet database, Conference Papers Index, AIDS and Cancer Research Abstracts, and ClinicalTrials.gov. We also scanned the reference lists of articles. We only included trials in which individuals were randomly allocated to receive treatment. Two reviewers independently applied the criteria for trial selection, assessed trial quality, and extracted data. RESULTS: Five trials comprising 1926 adults from Hong Kong, Spain, and Uganda were identified. The mean duration of follow-up varied from 13 to 37 months. Overall, development of active tuberculosis was equivalent in association with both regimens (pooled risk difference, 0%; 95% confidence interval [CI], -1% to 2%; percentage of total variation across the studies that is the result of heterogeneity rather than chance [I2], 0%; P=.86). Severe adverse effects were reported with a similar frequency for both regimens (pooled risk difference, -1%; 95% CI, -7% to 5%) but with statistically significant heterogeneity detected (I2, 78%; P=.001). However, a subanalysis of high-quality trials (including 74% of the sample size) suggested that both regimens were equally safe. In 3 trials (comprising 1390 patients) that provided data on mortality, the regimens showed equivalence (pooled risk difference, -1%; 95% CI, -4% to 2%; I2, 2.7%; P=.38). CONCLUSION: Short-course therapy with rifampin plus isoniazid was equivalent to standard therapy with isoniazid in terms of efficacy, the proportion of severe side effects that occurred, and mortality.

Antitubercular Agents↗

PubMed2002

[Inhaled nitric oxide in the peroperative period and recovery].

OBJECTIVE: To analyse the current knowledge concerning use of inhaled NO (iNO) in anaesthesia and intensive care. DATA SOURCE: References were obtained from Medline, recent review articles, the library of the department and personal files. STUDY SELECTION: All categories of articles on this topic have been selected. DATA EXTRACTION: Articles have been analysed for history, biochemistry, pharmacology, toxicity and clinical use of iNO. DATA SYNTHESIS: Nitric oxide (NO) is a potent endothelium-dependent vasodilator. Because of its selective action on pulmonary circulation and the lack of effect on the systemic circulation due to its inactivation by haemoglobin, iNO has been presented as a new therapeutic agent in most diseases with pulmonary hypertension. During heart transplantation or surgical correction of congenital heart disease, iNO decreases pulmonary hypertension and improves altered right ventricular function. Studies included however small numbers of patients. Preliminary pharmacological studies demonstrated that iNO was able to decrease pulmonary hypertension and improve systemic oxygenation in adult respiratory distress syndrome. To date, none of the three multicentric studies performed was able to show any significant effect on duration of mechanical ventilation, morbidity or mortality. Finally, the sole demonstrated indication for iNO which remains is the persistent pulmonary hypertension of the newborn. Two multicentric studies have evidenced an improvement in systemic oxygenation and a reduced need for extracorporeal membrane oxygenation. In these two studies global mortality was however unchanged. CONCLUSION: Persistent pulmonary hypertension is the sole demonstrated indication for iNO. Inhaled nitric oxide may be efficient in pulmonary hypertension, right ventricular dysfunction and severe hypoxemia. Inhaled nitric oxide must be considered as a rescue therapy or needs to be part of research protocols.

Administration, Inhalation↗

PubMed2006

Inhaled ciclesonide versus inhaled budesonide or inhaled beclomethasone or inhaled fluticasone for chronic asthma in adults: a systematic review.

BACKGROUND: Ciclesonide is a new inhaled corticosteroids licensed for the prophylactic treatment of persistent asthma in adults. Currently beclomethasone dipropionate, budesonide and fluticasone propionate are the most commonly prescribed inhaled corticosteroids for the treatment of asthma but there has been no systematic review comparing the effectiveness and safety ciclesonide to these agents. We therefore aimed to systematically review published randomised controlled trials of the effectiveness and safety of ciclesonide compared to alternative inhaled corticosteroids in people with asthma. METHODS: We performed literature searches on MEDLINE, EMBASE, PUBMED, the COCHRANE LIBRARY and various Internet evidence sources for randomised controlled trials or systematic reviews comparing ciclesonide to beclomethasone or budesonide or fluticasone in adult humans with persistent asthma. Data was extracted by one reviewer. RESULTS: Five studies met the inclusion criteria. Methodological quality was variable. There were no trials comparing ciclesonide to beclomethasone. There was no significant difference between ciclesonide and budesonide or fluticasone on the following outcomes: lung function, symptoms, quality of life, airway responsiveness to a provoking agent or inflammatory markers. However, the trials were very small in size, increasing the possibility of a type II error. One trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 47% of that of budesonide while another trial demonstrated that the combined deposition of ciclesonide (and its active metabolite) in the oropharynx was 53% of that of fluticasone. One trial demonstrated less suppression of cortisol in overnight urine collection after ciclesonide compared to fluticasone (geometric mean fold difference = 1.5, P < 0.05) but no significant difference in plasma cortisol response. CONCLUSION: There is very little evidence comparing CIC to other ICS, restricted to very small, phase II studies of low power. These demonstrate CIC has similar effectiveness and efficacy to FP and BUD (though equivalence is not certain) and findings regarding oral deposition and HPA suppression are inconclusive. There is no direct comparative evidence that CIC causes fewer side effects since none of the studies reported patient-based outcomes.

Administration, Inhalation↗

PubMed2005

Single dose oral rofecoxib for postoperative pain.

BACKGROUND: Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. So far, other similar anti-inflammatory drugs are unaffected. Further information is available at www.vioxx.com. Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that was licensed in the UK and the US for acute pain treatment and is associated with fewer gastrointestinal adverse events than conventional NSAIDs. Rofecoxib is believed to be at least as effective as conventional non-steroidal anti-inflammatory drugs (NSAIDs) for postoperative pain. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of rofecoxib for moderate to severe postoperative pain, and to compare its effectiveness with other analgesics used for treating acute pain. SEARCH STRATEGY: We searched Cochrane Library (Issue 1, 2002), MEDLINE (1966 to March 2002), Biological Abstracts (1985 to Dec 2001), CINAHL (1982 to Dec 2001), Psychinfo (1967 to Jan 2002), PubMed (March 2001) and the Oxford pain database. SELECTION CRITERIA: Randomised controlled trials of adult patients who received either rofecoxib or placebo for postoperative pain. DATA COLLECTION AND ANALYSIS: Trials were quality scored and the data extracted by two reviewers independently. Summed pain relief (TOTPAR) or pain intensity difference (SPID) was extracted and converted into dichotomous information yielding the number of patients with at least 50% pain relief. These derived results were used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS: Seven studies met the inclusion criteria. All the trials were funded by Merck & Company, the manufacturer of rofecoxib. In total, 667 patients were treated with rofecoxib 50 mg and 315 with placebo. The NNT for rofecoxib 50 mg was 2.2 (95% CI 1.9 to 2.4), ie, for every two patients treated with rofecoxib 50 mg, one patient experienced at least 50% pain relief that would not have done had they received placebo. All the studies were of short duration, and reported adverse events occurred less frequently with rofecoxib 50 mg than with placebo. AUTHORS' CONCLUSIONS: Rofecoxib 50 mg (a dose 2 to 4 times the standard daily dose for chronic pain) is an effective single dose oral analgesic for acute postoperative pain.

Administration, Oral↗

PubMed1999

Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase.

Catecholamine neurotransmitters are synthesized by hydroxylation of tyrosine to L-dihydroxyphenylalanine (L-Dopa) by tyrosine hydroxylase (TH). The elimination of TH in both pigmented and albino mice described here, like pigmented TH-null mice reported previously (Kobayashi et al., 1995; Zhou et al., 1995), demonstrates the unequivocal requirement for catecholamines during embryonic development. Although the lack of TH is fatal, TH-null embryos can be rescued by administration of catecholamine precursors to pregnant dams. Once born, TH-null pups can survive without further treatment until weaning. Given the relatively rapid half-life of catecholamines, we expected to find none in postnatal TH-null pups. Despite the fact that the TH-null pups lack TH and have not been supplemented with catecholamine precursers, catecholamines are readily detected in our pigmented line of TH-null mice by glyoxylic acid-induced histofluorescence at postnatal day 7 (P7) and P15 and quantitatively at P15 in sympathetically innervated peripheral organs, in sympathetic ganglia, in adrenal glands, and in brains. Between 2 and 22% of wild-type catecholamine concentrations are found in these tissues in mutant pigmented mice. To ascertain the source of the catecholamine, we examined postnatal TH-null albino mice that lack tyrosinase, another enzyme that converts tyrosine to L-Dopa but does so during melanin synthesis. In contrast to the pigmented TH-null mice, catecholamine histofluorescence is undetectable in postnatal albino mutants, and the catecholamine content of TH-null pups lacking tyrosinase is 18% or less than that of TH-null mice with tyrosinase. Thus, these extraordinary circumstances reveal that tyrosinase serves as an alternative pathway to supply catecholamines.

Adrenal Glands↗