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PubMed2005

Interventions for photodamaged skin.

BACKGROUND: Photodamage describes skin changes such as fine and coarse wrinkles, roughness, freckles and pigmentation changes that occur as a result of prolonged exposure to the sun. Many treatments are available to reverse the damage, but it is unclear which work and at what cost in terms of unwanted side effects. OBJECTIVES: To assess the effects of topically applied treatments, tablet treatments, laser and surgical procedures for photodamaged skin. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Issue 1 2002, MEDLINE (1966-June 2002), EMBASE (1974-June 2002), Health Periodicals (1976-June 2002). We checked references of articles and communicated with authors and the pharmaceutical industry. SELECTION CRITERIA: Randomised controlled trials which compared drug or surgical interventions with no treatment, placebo or another drug, in adults with mild, moderate or severe photodamage of the face or forearms. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Thirty studies of variable quality were included. Eight trials showed that topical tretinoin cream, in concentrations of 0.02% or higher, was superior to placebo for participants with mild to severe photodamage on the face and forearms (although losses to follow-up were relatively high in most studies). For example, the relative risk of improvement for 0.05% tretinoin cream, compared to placebo (three studies), at 24 weeks, was 1.73 (95% confidence interval 1.39 to 2.14). This effect was not seen for 0.001% topical tretinoin (one study) or 0.01% (three studies). A dose-response relationship was evident for both effectiveness and skin irritation. One small within-patient study showed benefit from topical ascorbic acid compared with placebo. Tazarotene (0.01% to 0.1%) and isotretinoin (0.1%) both showed significant improvement over placebo for moderate photodamage (one study each). There is limited evidence (one trial), to show that the effectiveness of 0.05% tretinoin, is equivalent to the effects of 0.05% and 0.1% tazarotene. One small study showed greater improvement in upper lip wrinkles with CO2 laser technique compared to Baker's phenol chemical peel, at 6 months. Three small RCTs comparing CO2 laser with dermabrasion found no difference in wrinkle score at 4 to 6 months, suggesting that both methods are equally efficacious, but more erythema was reported with the laser. The effectiveness of other interventions such as hydroxy acids and natural polysaccharides was not clear. AUTHORS' CONCLUSIONS: There is conclusive evidence that topical tretinoin improves the appearance of mild to moderate photodamage on the face and forearms, in the short term. However erythema, scaling/dryness, burning/stinging and irritation may be experienced initially. There is limited evidence that tazarotene and isotretinoin benefit patients with moderate photodamage on the face: both are associated with skin irritation and erythema. The effectiveness of other interventions remains uncertain.

Administration, Cutaneous↗
PubMed2006

Misoprostol compared with prostaglandin E2 for labour induction in women at term with intact membranes and unfavourable cervix: a systematic review.

BACKGROUND: Misoprostol is a commonly used prostaglandin to induce labour. A potential risk of induction, however, is caesarean delivery, especially in women with an unfavourable cervix. OBJECTIVES: To evaluate the use of misoprostol, compared with prostaglandin E2 (PgE2), for labour induction in women at term with an unfavourable cervix and intact membranes. SEARCH STRATEGY: PubMed, Medline, EMBASE and the Cochrane Library were searched for articles published in any language from January 1987 to December 2005, using the keywords 'misoprostol', 'labour/labor' and 'induction'. SELECTION CRITERIA: We identified randomised trials of women at term (> or =37 weeks of gestation) with intact membranes and unfavourable cervix, undergoing labour induction with misoprostol, orally, vaginally, sublingually or buccally, compared with PgE2 vaginally or intracervically. DATA COLLECTION AND ANALYSIS: Caesarean delivery was the primary outcome, with tachysystole and hyperstimulation as secondary outcomes. The primary analysis compared any misoprostol with any PgE2 for all women, with a subgroup analysis for nulliparous women. Secondary analyses compared different routes and doses of misoprostol (oral or vaginal and 25 microgram or >25 microgram) and PgE2 (intracervical or vaginal). Relative risks (RR) and 95% confidence intervals (CI) were calculated using random effects models. Main results Fourteen of 611 articles identified met the criteria for systematic review, with three providing information for nulliparous women. There was no difference in the risk of caesarean delivery between misoprostol and PgE2 groups (RR = 0.99, 95% CI = 0.83-1.17). Any misoprostol was associated with higher risks of tachysystole and hyperstimulation compared with any PgE2 (RR = 1.86, 95% CI = 1.01-3.43 and RR = 3.71, 95% CI = 2.00-6.88, respectively). There was a higher rate of vaginal delivery within 24 hours among all vaginal deliveries with any misoprostol compared with any PgE2 (RR = 1.14, 95% CI = 1.00-1.31), and among all deliveries, a lower rate of oxytocin use (RR = 0.71, 95% CI = 0.60-0.85) but a trend towards increased meconium staining was observed (RR = 1.22, 95% CI = 0.96-1.55). The use of misoprostol at starting dosages >25 microgram had similar findings to the primary analysis. Studies of lower misoprostol dosing (starting dose of 25 microgram) did not show any differences in the outcomes of interest, but the sample size of this secondary analysis was small (304 women, 155 receiving misoprostol). AUTHOR'S CONCLUSIONS: Although misoprostol in women at term with an unfavourable cervix and intact membranes was more effective than PgE2 in achieving vaginal delivery within 24 hours, misoprostol does not reduce the rate of caesarean delivery either in all women or in the subgroup of nulliparous women, and it increases the rates of tachysystole and hyperstimulation. Further studies of misoprostol using a starting dose of 25 microgram may be warranted.

Administration, Intravaginal↗
PubMed2005

Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.

BACKGROUND: Non-valvular atrial fibrillation (AF) is associated with an increased risk of stroke mediated by embolism of stasis-precipitated thrombi from the left atrial appendage. OBJECTIVES: The objective is to characterize the efficacy and safety of oral anticoagulants (OACs) for the primary prevention of stroke in patients with chronic AF. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched in June 2004). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2004), MEDLINE (1966 to June 2004), and the reference lists of recent review articles. We also contacted the Atrial Fibrillation Collaboration and experts working in the field to identify unpublished and ongoing trials. SELECTION CRITERIA: All randomized controlled trials comparing OACs with control in patients with chronic non-valvular atrial fibrillation and no history of transient ischemic attack (TIA) or stroke. DATA COLLECTION AND ANALYSIS: Trials for inclusion were independently selected by two authors who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, intention-to-treat. Since the published results of four trials included 3% to 8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators. MAIN RESULTS: Of 2313 participants without prior cerebral ischemia from five randomized trials, the mean age was 69 years. Participant features and study quality were similar between trials: the OAC in all five trials was warfarin. About half of participants (n = 1154) were randomized to adjusted-dose warfarin with mean achieved INRs ranging between 2.0 to 2.6. During 1.5 years mean follow up, warfarin was associated with large, highly statistically significant reductions in all strokes (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.26 to 0.59), ischemic stroke (OR 0.34, 95% CI 0.23 to 0.52), all disabling or fatal stroke (OR 0.47, 95% CI 0.28 to 0.80), death (OR 0.69, 95% CI 0.50 to 0.94) and the combined endpoint of all stroke, myocardial infarction or vascular death (OR 0.56, 95% CI 0.42 to 0.76). The observed rates of intracranial and extracranial hemorrhage were not significantly increased by OAC therapy, but the confidence intervals were wide. AUTHORS' CONCLUSIONS: Treatment with adjusted-dose warfarin to achieved INRs of 2 to 3 reduces stroke, disabling or fatal stroke, and death for patients with non-valvular AF. The benefits were not substantially offset by increased bleeding among these participants in randomized clinical trials. Limitations include relatively short follow up and imprecise estimates of bleeding risks from the selected participants enrolled in the trials. For primary prevention of stroke in AF patients, about 25 strokes and about 12 disabling or fatal strokes would be prevented yearly for every 1000 atrial fibrillation patients given OACs.

Administration, Oral↗
PubMed2006

Systemic antibiotics versus topical treatments for chronically discharging ears with underlying eardrum perforations.

BACKGROUND: Chronic suppurative otitis media (CSOM) causes ear discharge and impairs hearing. OBJECTIVES: To compare systemic antibiotics and topical antiseptics or antibiotics (excluding steroids) for treating chronically discharging ears with an underlying eardrum perforation (CSOM). SEARCH STRATEGY: The Cochrane ENT Disorders Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 1, 2005), MEDLINE (January 1951 to March 2005), EMBASE (January 1974 to March 2005), LILACS (January 1982 to March 2005), AMED (1985 to March 2005), CINAHL (January 1982 to March 2005), OLDMEDLINE (January 1958 to December 1965) PREMEDLINE, Metadatabase of registers of ongoing trials (mRCT), and article references. SELECTION CRITERIA: Randomised controlled trials; any systemic versus topical treatment (excluding steroids); participants with CSOM. DATA COLLECTION AND ANALYSIS: One author assessed eligibility and quality, extracted data, entered data into RevMan; two authors provided a second assessment of titles and abstracts, and inputted where there was ambiguity. We contacted investigators for clarifications. MAIN RESULTS: Nine trials (833 randomised participants; 842 analysed participants or ears). CSOM definitions and severity varied; some included mastoid cavity infections, other diagnoses, or complications. Methodological quality varied; generally poorly reported, follow-up short, handling of bilateral disease inconsistent. Topical quinolone antibiotics were better than systemic antibiotics at clearing discharge at 1-2 weeks: relative risks (RR) were, 3.21 (95% confidence interval (CI) 1.88 to 5.49) using systemic non-quinolone antibiotics (2 trials, N = 116), and 3.18 (1.87 to 5.43) using systemic quinolone (3 trials, N = 175); or 2.75 (1.38 to 5.46) in favour of systemic plus topical quinolone over systemic quinolone alone (2 trials, N = 90). No statistically significant benefit was seen at 2-4 weeks for topical non-quinolone antibiotic (without steroids) or topical antiseptic over systemic antibiotics (mostly non-quinolones), but numbers were small: one trial tested topical non-quinolones (N = 31); two tested antiseptics (N = 152). No benefit of adding systemic to topical treatment at 1-2 weeks was detected either, although evidence was limited (three trials, N = 204). Evidence regarding safety was generally weak. Adverse events reported were generally mild, although hearing worsened by ototoxicity (damaging auditory hair cells) was seen with chloramphenicol drops (non-quinolone antibiotic). AUTHORS' CONCLUSIONS: Topical quinolone antibiotics can clear aural discharge better than systemic antibiotics; topical non-quinolone antibiotic (without steroids) or antiseptic results are less clear. Evidence regarding safety was weak. Further studies should clarify topical non-quinolones and antiseptic effectiveness, assess longer-term outcomes (for resolution, healing, hearing, or complications), and include further safety assessments, particularly to clarify the risks of ototoxicity and whether there may be fewer adverse events with topical quinolones than other topical or systemic treatments.

Administration, Oral↗
PubMed2000

Three- or four- versus two-drug antiretroviral maintenance regimens for HIV infection.

BACKGROUND: Combination antiretroviral therapy administered to HIV-infected individuals has been shown to improve immunologic function and delay the progression of HIV infection. However, because patient adherence to complicated combination-therapy antiretroviral regimens is difficult and because of concerns regarding cumulative toxicity of antiretroviral drugs, regimens that utilize fewer antiretroviral agents are desirable. OBJECTIVES: To compare the use three- or four- versus two-drug antiretroviral maintenance regimens following successful induction therapy for HIV infection. SEARCH STRATEGY: The following electronic databases were searched for relevant randomized trials or reviews: 1. MEDLINE for the years 1982-1999 using the search terms human immunodeficiency virus, antiretroviral therapy, maintenance therapy, zidovudine, lamivudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, AIDS, anti-HIV agents, HIV infection and HIV seropositivity 2. AIDSLINE for the years 1982-1999 using the search terms antiretroviral therapy, maintenance therapy, zidovudine, lamidvudine, indinavir, stavudine, saquinivir, nelfinavir, didanosine, zalcitabine, ritonovir, anti-HIV agents 3. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness and the Cochrane Clinical Trials Register in the Cochrane Library, Issue 2, 1999. 4. The specialist register of trials maintained by the Cochrane Collaborative Review Group on HIV Infection and AIDS 5. AIDSTRIALS, a specialist registry of current and completed trials maintained by the U.S. National Library of Medicine The abstracts of relevant conferences, including the International Conferences on AIDS, the Conference on Retroviruses and Opportunistic Infections, the Infectious Disease Society of America annual meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy, as indexed by AIDSLINE, were also reviewed. All reference lists of all review articles and primary articles identified were searched. SELECTION CRITERIA: Randomized controlled trials in which HIV-infected adults who had successfully completed three- or four-drug antiretroviral induction therapy were randomized to maintenance therapy with three or four drugs or maintenance therapy with two drugs. Successful induction therapy was defined by a plasma viral load of less than 500 copies/ml. DATA COLLECTION AND ANALYSIS: Two reviewers assessed eligibility and trial quality. Attempts were made to contact the authors of the included abstract. Data on the number of patients experiencing loss of viral suppression were abstracted by two reviewers. The data were pooled, where appropriate, to yield odds ratios, using random effects models. MAIN RESULTS: Four trials were identified including three published studies and one abstract. Compared to three- or four-drug maintenance therapy, maintenance therapies including fewer drugs were associated with a higher risk of virologic failure (loss of HIV suppression to non-detectable levels). Combining the results of all four studies yielded an odds ratio of 5.55 (95% confidence interval, 3.14 - 9.80). Similar results were obtained when the one abstract was excluded (odds ratio, 5.48; 95% confidence interval, 2.82 - 10.65). Performing subgroup analyses of studies using the same induction and maintenance regimens gave similar results. Maintenance regimens of zidovudine and lamivudine compared to maintenance regimens with zidovuine, lamivudine and indinavir, were associated with significantly higher rates of virologic failure (odds ratio, 4.57; 95% confidence interval, 1.80 - 11.58). Similarly, maintenance regimens that discontinued one or more protease inhibitor after including them in induction therapy were also associated with a significantly higher risk of virologic failure (odds ratio, 6.15; 95% confidence interval, 3.40 -11.10). (ABSTRACT TRUNCATED)

Anti-HIV Agents↗
PubMed2001

Beclomethasone at different doses for chronic asthma (review).

BACKGROUND: Beclomethasone dipropionate (BDP) is available in a wide range of daily doses for the treatment of long-term asthma. OBJECTIVES: To assess the evidence for a dose response relationship for BDP in the treatment of long-term asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trial register, Cochrane Controlled Trials Register (The Cochrane Library issue 1 1999) and references lists of articles. Authors and Glaxo Wellcome UK were contacted to identify eligible studies. We also hand searched the proceeding from relevant respiratory society meetings, the British Journal of Clinical Research and the European Journal of Clinical Research for studies. SELECTION CRITERIA: Prospective, randomised trials comparing two or more daily doses of BDP in patients over the age of two years with long-term asthma. DATA COLLECTION AND ANALYSIS: Trials were selected for inclusion and scored for quality by two reviewers. Data were extracted by one reviewer. Authors were contacted to clarify details of study design and retrieve missing data. MAIN RESULTS: 11 trials involving 1614 subjects were included. Methodological quality was variable. Studies rarely gave a clear indication of the degree of asthma control at baseline. Less than two-fold to five-fold dose differences were assessed by different studies. The results are reported as weighted mean differences (WMD) with 95% confidence limits (95% CI). The number of trials (N) contributing to each outcome is stated. In non-oral steroid treated asthmatics a small advantage of BDP 800 mcg/d over 400 mcg/d was apparent for improvement in morning peak expiratory flow rate (PEFR) compared to baseline, WMD 11 L/min (95% CI 4 to 19 L/min) N=2; improvement in forced expired volume in one second (FEV1) compared to baseline, WMD 9 ml (95% CI 3 to 140) N=1; and reduction in night-time symptom score compared to baseline, WMD 0.13 (95% CI 0.04 to 0.22) N=1. Studies that assessed BDP 1000 v 500 mcg/d and BDP 1600 v 400 mcg/d demonstrated significant advantage of higher dose over lower dose for histamine bronchial hyper-responsiveness (BHR) and percentage improvement in FEV1 compared to baseline. No differences between higher and lower daily doses of BDP were apparent for daytime symptoms, withdrawals due to asthma exacerbation, oropharyngeal side effects or measures of hypothalamo-pituitary-adrenal (HPA) function. No difference in prednisolone sparing effect was apparent when comparing high dose and low dose BDP in oral corticosteroid (OCS) dependent patients. REVIEWER'S CONCLUSIONS: BDP appears to demonstrate a shallow dose response effect in long-term asthma for a small number of efficacy outcomes over range of daily doses from 400 mcg/d to 1600 mcg/d, although the clinical significance of the improvements afforded by higher doses is questionable.

Administration, Inhalation↗
PubMed2006

Oral steroids for adhesive capsulitis.

BACKGROUND: This review is one in a series of Cochrane reviews of interventions for shoulder pain in adults. OBJECTIVES: To determine the efficacy and safety of oral steroids for adhesive capsulitis. SEARCH STRATEGY: Searches of the Cochrane Library including CENTRAL, Issue 4, 2005, Cochrane Musculoskeletal Review Group Register, MEDLINE, EMBASE, CINAHL were conducted in November 2005, unrestricted by date or language. SELECTION CRITERIA: Only studies described as randomised controlled trials studying participants with adhesive capsulitis, frozen shoulder, stiff painful shoulder or periarthritis and interventions of oral steroids compared to placebo, no treatment, or any other treatment were included. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed methodological quality of each included trial and extracted data. Standard Cochrane methodology was used to analyse the extracted data. MAIN RESULTS: Five small trials were included: two trials (30 and 49 participants) of oral steroids or placebo; one trial (40 participants) of oral steroids or no treatment; one trial (28 participants) of oral or intra-articular steroids; and one trial (32 participants) of manipulation under anaesthesia and intraarticular steroid injection with or without oral steroids. Study participants were similar across trials, but no trial used the same oral steroid regimen or dosage. Trials were of variable quality (only one of high quality) and some were poorly reported. No meta-analyses could be performed as no raw data could be extracted from one placebo-controlled trial and three trials used different comparators. One trial reported significant short-term benefits of oral steroids versus placebo: 48% more participants reported success (RR = 2 (95% CI 1.3 to 3.1, NNT=2); overall improvement in pain 2.7 (95% CI 1.4 to 4.0) on a 0 to 10 point scale; total shoulder abduction increased by 23.3 degrees (95% CI 11.3 to 35.3); Shoulder Pain and Disability Index (SPADI) score improved by 18.1 (95% CI 7.6 to 28.6) on a 0 to 100 point scale. But benefits were not maintained at 6 weeks. A second trial reported no significant differences between oral steroid and placebo in pain or range of movement but it suggested improvement occurred earlier in the steroid treated group. A third trial reported that oral steroids provided a more rapid initial improvement in pain compared to no treatment but negligible differences by five months. There were minimal adverse effects reported. AUTHORS' CONCLUSIONS: Available data from two placebo-controlled trials and one no-treatment controlled trial provides "Silver" level evidence (www.cochranemsk.org) that oral steroids provides significant short-term benefits in pain, range of movement of the shoulder and function in adhesive capsulitis but the effect may not be maintained beyond six weeks.

Administration, Oral↗
PubMed2005

Interventions to enhance medication adherence.

BACKGROUND: People who are prescribed self-administered medications typically take less than half the prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications, but also might increase their adverse effects. OBJECTIVES: To update a review summarizing the results of randomized controlled trials (RCTs) of interventions to help patients follow prescriptions for medications for medical problems, including mental disorders but not addictions. SEARCH STRATEGY: Computerized searches were updated to September 2004 without language restriction in MEDLINE, EMBASE, CINAHL, The Cochrane Library, International Pharmaceutical Abstracts (IPA), PsycINFO and SOCIOFILE. We also reviewed bibliographies in articles on patient adherence and articles in our personal collections, and contacted authors of original and review articles on the topic. SELECTION CRITERIA: Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings. DATA COLLECTION AND ANALYSIS: Study design features, interventions and controls, and results were extracted by one reviewer and confirmed by at least one other reviewer. We extracted adherence rates and their measures of variance for all methods of measuring adherence in each study, and all outcome rates and their measures of variance for each study group, as well as levels of statistical significance for differences between study groups, consulting authors and verifying or correcting analyses as needed. MAIN RESULTS: For short-term treatments, four of nine interventions reported in eight RCTs showed an effect on both adherence and at least one clinical outcome, while one intervention reported in one RCT significantly improved patient compliance, but did not enhance the clinical outcome. For long-term treatments, 26 of 58 interventions reported in 49 RCTs were associated with improvements in adherence, but only 18 interventions led to improvement in at least one treatment outcome. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Six studies showed that telling patients about adverse effects of treatment did not affect their adherence. AUTHORS' CONCLUSIONS: Improving short-term adherence is relatively successful with a variety of simple interventions. Current methods of improving adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. High priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders.

Drug Therapy↗
PubMed2003

Oral sumatriptan for acute migraine.

BACKGROUND: Migraine is a common neurovascular disorder characterized by recurrent episodes of disabling headache, autonomic nervous system dysfunction, and, in some patients, neurological aura symptoms. Sumatriptan is one of a class of selective serotonin 5-hydroxytryptamine (5-HT1B/1D) agonists (triptans) thought to relieve migraine attacks by several mechanisms, including cranial vasoconstriction and peripheral and central neural inhibition. OBJECTIVES: To describe and assess the evidence from randomized controlled trials (RCTs) concerning the efficacy and tolerability of oral sumatriptan for the treatment of a single acute attack of migraine in adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2001), MEDLINE (1966 through November 2001), and reference lists of articles and books. SELECTION CRITERIA: We included double-blind RCTs comparing oral sumatriptan (100 mg, 50 mg, 25 mg) with placebo, no intervention, other drug treatments, behavioral therapy, or physical therapy for the treatment of an acute attack of migraine in adults. Trials comparing different doses of sumatriptan or dosing regimens were also included. Outcomes considered were: 2-hour pain-free response, headache relief/headache intensity, and functional disability; headache recurrence; and adverse events. DATA COLLECTION AND ANALYSIS: Data were abstracted by one reviewer and over-read by the other. The two reviewers independently assessed trial quality. Information on adverse events was collected from trial reports. MAIN RESULTS: Twenty-five trials involving 16,200 participants were included. Methodological quality was generally good. Sixteen trials were placebo comparisons and showed that sumatriptan in doses of 100 mg (14 trials), 50 mg (five trials), and 25 mg (three trials) provided significantly better pain-free response (100 mg and 25 mg only), headache relief, and relief of disability at 2 hours. Numbers-needed-to-treat (NNTs) for pain-free response at 2 hours were 5.1 (3.9 to 7.1) for the 100-mg dose (n = 2221) and 7.5 (2.7 to 142) for the 25-mg dose (n = 131); there was no significant difference between the 50-mg dose and placebo for this outcome (n = 127). For headache relief at 2 hours, NNTs were 3.4 (3.0 to 4.0), 3.2 (2.4 to 5.1), and 3.4 (2.3 to 6.6) for sumatriptan 100 mg (n = 2940), 50 mg (n = 420), and 25 mg (n = 226), respectively. Precise estimates of the efficacy of the 50- and 25-mg doses relative to the 100-mg dose could not be obtained. Adverse events were more common with sumatriptan 100 mg than with placebo (risk difference [RD] = 0.14 [0.09 to 0.20]; number-needed-to-harm [NNH] = 7.1 [5.0 to 11.1]; n = 3172). RDs for the 50- and 25-mg vs. placebo comparisons were not statistically significant. REVIEWER'S CONCLUSIONS: Oral sumatriptan has been shown to be an effective drug for the treatment of a single acute attack of migraine. It is well tolerated, though minor adverse events were not uncommon in the included trials. Other triptans were generally similar in efficacy and adverse events. Among non-triptan drugs, ergotamine + caffeine was significantly less effective than sumatriptan, and other drugs have been insufficiently studied to draw firm conclusions.

Administration, Oral↗
PubMed2000

Vasoactive drugs for acute stroke.

BACKGROUND: It is unclear whether blood pressure should be managed after acute stroke and if so whether it is best to reduce or increase blood pressure. OBJECTIVES: The objective of this review was to assess the effect of lowering or elevating blood pressure in people with acute stroke, and the effect of different vasoactive drugs on blood pressure in acute stroke. SEARCH STRATEGY: We searched the Cochrane Library (1999 Issue 1) using the CDSR and the CCTR databases, MEDLINE (from 1966), EMBASE (from 1980), BIDS ISI (Science Citation Index from 1981), and existing review articles. We contacted researchers in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised trials of interventions that would be expected, on pharmacological grounds, to alter blood pressure in patients within two weeks of the onset of acute ischaemic or haemorrhagic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the trial inclusion criteria, assessed trial quality, and extracted the data. MAIN RESULTS: Sixty five trials were identified involving in excess of 11,500 patients; a further 5 trials are ongoing. Data were obtained for 32 trials (5,368 patients). Significant imbalances in baseline blood pressure were present across trials of intravenous calcium channel blockers and prostacyclin. Major imbalances in baseline blood pressure between treatment and control groups have made the interpretation of these results difficult. Intravenous calcium channel blockers (CCBs) and oral CCBs significantly lowered late blood pressure as compared to controls. (systolic/diastolic BP): iv CCBs -8.2/-6.7 mm Hg (95% CI -12.6 to -3.8)/ (95% CI -9.2 to -4.3); oral CCBs -3.2/-2.1 mm Hg (95% CI -5.0 to -1.3)/ (95% CI -3.0 to -1.0). Beta blockers significantly lowered late diastolic blood pressure but not significantly late systolic blood pressure; -5.0/-4.5 mm Hg (95% CI -10.2 to 0.4)/(95% CI -7.8 to -1.15). Angiotensin converting enzyme inhibitors and prostacyclin non-significantly reduced late BP as compared to the controls by -5.4/-3.0 mm Hg (95% CI -16.5 to 5.8)/(95% CI -11.1 to 5.0) and -7.4/-3.9 mmHg (95% CI -15.6 to 0.2)/(95% CI -8.1 to 0.4) respectively. Magnesium, naftidrofuryl and piracetam had no significant effect on blood pressure. Oral CCBs and beta blockers each significantly reduced late heart rate (beats per minute (bpm)): CCBs -2.8 bpm (95%CI -3.9 to -1.7); beta blockers -9.3 bpm (95% CI -12.0 to -6.6). Prostacyclin significantly increased late heart rate by +5.6 bpm (95% CI 0.8 to 10.4). None of the drug classes significantly altered outcome apart from beta blockers and streptokinase which increased early case fatality (odds ratio 1.77, 95%CI, 1.05 to 3.00) and 2.27 (95% CI 1.4 to 3.67). REVIEWER'S CONCLUSIONS: There is not enough evidence reliably to evaluate the effect of altering blood pressure on outcome after acute stroke. CCBs, beta blockers, and probably ACE-inhibitors, prostacyclin and nitric oxide, each lowered BP during the acute phase of stroke. In contrast, magnesium, naftidrofuryl and piracetam had little or no effect on BP.

Administration, Oral↗
PubMed1999

The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a metaanalysis of randomized clinical trials.

STUDY OBJECTIVE: This study was conducted to determine whether the addition of inhaled ipratropium to inhaled beta-agonist therapy is effective in the treatment of adults with acute asthma exacerbation. METHODS: Published reports of randomized, controlled trials assessing the use of ipratropium and beta-agonists in asthma were identified by a search of the MEDLINE, EMBASE, CINAHL, Biological Abstracts on CD, the Cochrane Library, and Current Contents databases. Bibliographies from identified studies and from review articles were manually searched. Published and unpublished reports in English, French, and Italian were identified and assessed for inclusion in the metaanalysis. Randomized, double-blind, placebo-controlled trials were selected in which ipratropium was used as adjunctive therapy to beta-agonists in adult patients with acute asthma exacerbation presenting to a hospital emergency department or similar acute care setting. Data were extracted independently by 2 reviewers. For eligible trials, the mean percent change in peak expiratory flow rate (PEFR), or forced expiratory volume in one second (FEV1), and their SDs were assessed in the ipratropium-treated and control groups. The effect of ipratropium on hospitalization rates and adverse effects were also analyzed. RESULTS: Data from 10 studies, reporting on a total of 1,377 patients with asthma, were pooled using a weighted average method. Compared with placebo, the use of ipratropium was associated with a pooled 7.3% improvement in FEV1 (95% confidence interval [CI] 3.8% to 10.9%), corresponding to an absolute improvement in FEV1 in the ipratropium/ beta-agonist group, which was 100 mL (95% CI 50 to 149 mL) above that seen for the group that received beta-agonist without ipratropium. Similarly, the pooled estimate of treatment effect in trials that reported data as PEFR was 22.1% (95% CI 11.0% to 33.2%), corresponding to an absolute peak expiratory flow improvement of 32 L/min (95% CI 16 to 47 L/min) in favor of the ipratropium/ beta-agonist combination group. When these data were combined using effect size as a common measure, the use of ipratropium was associated with a summary effect size of.38 (95% CI.27 to.48). Effect sizes were negatively correlated with baseline mean expiratory flows, suggesting that studies enrolling patients with more severe airflow obstruction showed greater absolute benefits of combination bronchodilator therapy. For the 3 trials reporting hospital admission data (n=1,031), patients receiving ipratropium had a relative risk of hospitalization of .73 (95% CI.53 to .99). The use of ipratropium was not associated with any severe adverse effects when used in conjunction with beta2 -agonists. CONCLUSION: There is a modest statistical improvement in airflow obstruction when ipratropium is used as an adjunctive treatment to beta2 -agonists for the treatment of acute asthma exacerbation. Although the clinical significance of this improvement in airflow obstruction remains unclear, it would seem reasonable to recommend the use of combination ipratropium/ beta-agonist therapy in acute adult asthmatic exacerbations, since the addition of ipratropium seemed to provide physiologic evidence of benefit without risk of adverse effects.

Acute Disease↗
PubMed2004

Inhaled insulin in diabetes mellitus.

BACKGROUND: Insulin therapy often relies on multiple daily injections of insulin. However this is a considerable burden to many people with diabetes and adherence to such an insulin regimen can be difficult to maintain, hence compromising optimal glycaemic control. Also, short acting injected insulin is absorbed more slowly than insulin released by the normal pancreas in response to a meal. Inhaled insulin has the potential to reduce the number of injections to perhaps one long-acting insulin per day, and provide a closer match to the natural state, by more rapid absorption from the lung. OBJECTIVES: To compare the efficacy, adverse effects and patient acceptability of inhaled versus injected insulin. SEARCH STRATEGY: A sensitive search strategy for randomised controlled or cross-over trials was combined with key terms for inhaled insulins. Databases searched were: The Cochrane Library, MEDLINE, PubMed, EMBASE, Science Citation Index, BIOSIS, Web of Science Proceedings, National Research Register UK, Current Controlled Trials, ClinicalTrials.gov, Conference Papers Index, LexisNexis, and web sites of the ADA and EASD were searched for recent meeting abstracts. Reference lists and journals were handsearched. There were no language restrictions on searching. Manufacturers of inhaled insulin were also contacted. Date of last search October 2002. SELECTION CRITERIA: Only randomised controlled trials with parallel groups or controlled cross-over trials, including type 1 or type 2 diabetic patients of any age treated with insulin, were considered eligible. The minimum trial duration considered was 10 weeks, as this is the time taken for glycated haemoglobin to reliably reflect changes in glycaemic control. DATA COLLECTION AND ANALYSIS: Trial selection and evaluation of study quality was performed independently by two reviewers. The quality of reporting of each trial was assessed according to a modification of the criteria outlined in Centre for Reviews and Dissemination (CRD) Report 4, Spitzer; and Jadad. MAIN RESULTS: Six randomised controlled trials were found and the overall number of participants was 1191. Three trials included patients with type 1 diabetes and three with type 2 diabetes. Three trials had a duration of 24 weeks, and three of 12 weeks. All were open label. There was insufficient information to determine the study quality. Results for HbA1c were similar for all trials, in that all showed comparable glycaemic control for inhaled insulin compared to an entirely subcutaneous regimen. All trials that reported patient satisfaction and quality of life showed that these were significantly greater in the inhaled insulin group. Overall there was no difference in total hypoglycaemic episodes between the groups, but one trial showed a statistically significant increase in severe hypoglycaemic episodes for the inhaled insulin group. No adverse pulmonary effects were observed in any of the studies, but longer follow-up will be required to be sure that there are no adverse side-effects. Cavets include: few studies published in full (so quality could not be assessed), and only two studies used the same basal regimen in both the inhaled and injected groups. REVIEWERS' CONCLUSIONS: Inhaled insulin taken before meals, in conjunction with an injected basal insulin, has been shown to maintain glycaemic control comparable to that of patients taking multiple daily injections. The key benefit appears to be that patient satisfaction and quality of life are significantly improved, presumably due to the reduced number of daily injections required. However, the patient satisfaction data is based on five trials, of which only two have been published in full; also the three trials containing quality of life data are all only published in abstract form at present. In addition, longer term pulmonary safety data are still needed. Also, the lower bioavailability, and hence higher doses of inhaled insulin required, may make it less cost-effective than injected insulin.

Administration, Inhalation↗
PubMed2003

Inhaled insulin in diabetes mellitus.

BACKGROUND: Insulin therapy often relies on multiple daily injections of insulin. However this is a considerable burden to many people with diabetes and adherence to such an insulin regimen can be difficult to maintain, hence compromising optimal glycaemic control. Also, short acting injected insulin is absorbed more slowly than insulin released by the normal pancreas in response to a meal. Inhaled insulin has the potential to reduce the number of injections to perhaps one long-acting insulin per day, and provide a closer match to the natural state, by more rapid absorption from the lung. OBJECTIVES: To compare the efficacy, adverse effects and patient acceptability of inhaled versus injected insulin. SEARCH STRATEGY: A sensitive search strategy for randomised controlled or cross-over trials was combined with key terms for inhaled insulins. Databases searched were: The Cochrane Library, MEDLINE, PubMed, EMBASE, Science Citation Index, BIOSIS, Web of Science Proceedings, National Research Register UK, Current Controlled Trials, ClinicalTrials.gov, Conference Papers Index, LexisNexis, and web sites of the ADA and EASD were searched for recent meeting abstracts. Reference lists and journals were handsearched. There were no language restrictions on searching. Manufacturers of inhaled insulin were also contacted. Date of last search October 2002. SELECTION CRITERIA: Only randomised controlled trials with parallel groups or controlled cross-over trials, including type 1 or type 2 diabetic patients of any age treated with insulin, were considered eligible. The minimum trial duration considered was 10 weeks, as this is the time taken for glycated haemoglobin to reliably reflect changes in glycaemic control. DATA COLLECTION AND ANALYSIS: Trial selection and evaluation of study quality was performed independently by two reviewers. The quality of reporting of each trial was assessed according to a modification of the criteria outlined in Centre for Reviews and Dissemination (CRD) Report 4, Spitzer; and Jadad. MAIN RESULTS: Six randomised controlled trials were found and the overall number of participants was 1191. Three trials included patients with type 1 diabetes and three with type 2 diabetes. Three trials had a duration of 24 weeks, and three of 12 weeks. All were open label. There was insufficient information to determine the study quality. Results for HbA1c were similar for all trials, in that all showed comparable glycaemic control for inhaled insulin compared to an entirely subcutaneous regimen. All trials that reported patient satisfaction and quality of life showed that these were significantly greater in the inhaled insulin group. Overall there was no difference in total hypoglycaemic episodes between the groups, but one trial showed a statistically significant increase in severe hypoglycaemic episodes for the inhaled insulin group. No adverse pulmonary effects were observed in any of the studies, but longer follow-up will be required to be sure that there are no adverse side-effects. Cavets include: few studies published in full (so quality could not be assessed), and only two studies used the same basal regimen in both the inhaled and injected groups. REVIEWER'S CONCLUSIONS: Inhaled insulin taken before meals, in conjunction with an injected basal insulin, has been shown to maintain glycaemic control comparable to that of patients taking multiple daily injections. The key benefit appears to be that patient satisfaction and quality of life are significantly improved, presumably due to the reduced number of daily injections required. However, the patient satisfaction data is based on five trials, of which only two have been published in full; also the three trials containing quality of life data are all only published in abstract form at present. In addition, longer term pulmonary safety data are still needed. Also, the lower bioavailability, and hence higher doses of inhaled insulin required, may make it less cost-effective than injected insulin.

Administration, Inhalation↗
PubMed2000

Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration.

BACKGROUND: Chronic wounds, including pressure sores, leg ulcers, diabetic foot ulcers and other kinds of wounds, healing by secondary intention are common in both acute and community settings. The prevention and treatment of chronic wounds includes many strategies, including the use of various wound dressings, bandages, antimicrobial agents, footwear, physical therapies and educational strategies. This review is one of a series of reviews, and focuses on the prevention and treatment of diabetic foot ulcers and the role of antimicrobial agents in chronic wounds in general. OBJECTIVES: To assess the clinical- and cost-effectiveness of (1) prevention and treatment strategies for diabetic foot ulcers and (2) systemic and topical antimicrobial agents in the prevention and healing of chronic wounds. METHODS - DATA SOURCES: Nineteen electronic databases were searched, including MEDLINE, CINAHL, Embase and the Cochrane Library. Relevant journals, conference proceedings and bibliographies of retrieved papers were hand-searched. An expert panel was consulted. METHODS - STUDY SELECTION: Randomised and non-randomised trials with a concurrent control group, which evaluated any intervention for the prevention or treatment of diabetic foot ulcers, or systemic or topical antimicrobials for chronic wounds (diabetic foot ulcers, pressure ulcers, leg ulcers of various aetiologies, pilonidal sinuses, non-healing surgical wounds, and cavity wounds) and used objective measures of outcome such as: (1) development or resolution of callus; (2) incidence of ulceration (for diabetic foot ulcer prevention studies); (3) incidence of pressure sores (pressure sore prevention studies); (4) any objective measure of wound healing (frequency of complete healing, change in wound size, time to healing, rate of healing); (5) ulcer recurrence rates; (6) side-effects; (7) amputation rates (diabetic foot ulcer treatment studies); (8) healing rates and recurrence of disease, among others, for pilonidal sinuses. Studies reporting solely microbiological outcomes were excluded. Decisions on the inclusion of primary studies were made independently by two reviewers. Disagreements were resolved through discussion. Data were extracted by one reviewer into structured summary tables. Data extraction was checked independently by a second reviewer and discrepancies resolved by discussion. All included studies were assessed against a comprehensive checklist for methodological quality. INCLUDED STUDIES - DIABETIC FOOT ULCERS: Thirty-nine trials which evaluated various prevention and treatment modalities for diabetic foot ulcers: footwear (2), hosiery (1), education (5), screening and foot protection programme (1); podiatry (1) for the prevention of diabetic foot ulcers; and footwear (1), skin replacement (2), hyperbaric oxygen (2), ketanserin (3), prostaglandins (3), growth factors (5), dressings and topical applications (9), debridement (2) and antibiotics (2) for the treatment of diabetic foot ulcers. INCLUDED STUDIES - ANTIMICROBIALS: Thirty studies were included, 25 with a randomised design. There were nine evaluations of systemic antimicrobials and 21 of topical agents. QUALITY OF STUDIES: The methodological and reporting quality was generally poor. Commonly encountered problems of reporting included lack of clarity about randomisation and outcome measurement procedures, and lack of baseline descriptive data. Common methodological weaknesses included: lack of blinded outcome assessment and lack of adjustment for baseline differences in important variables such as wound size; large loss to follow-up; and no intention-to-treat analysis. RESULTS - PREVENTION OF DIABETIC FOOT ULCERS: There is some evidence (1 large trial) that a screening and foot protection programme reduces the rate of major amputations. The evidence for special footwear (2 small trials) and educational programmes (5 trials) is equivocal. A single trial of podiatric care reported a significantly greater reduction in callus in patients receiving podiatric care. RESULTS - TREATMENT OF DIABETIC FOOT ULCERS: Total contact casting healed significantly more ulcers than did standard treatment in one study. There is evidence from 5 trials of topical growth factors to suggest that these, particularly platelet-derived growth factor, may increase the healing rate of diabetic foot ulcers. Although these studies were of relatively good quality, the sample sizes were far too small to make any definitive conclusions, and growth factors should be compared with current standard treatments in large, multicentre studies. Topical ketanserin increased ulcer healing rate in 2 studies, while systemic hyperbaric oxygen therapy reduced the rate of major amputations in 1 study. Preliminary research into the effects of iloprost and prostaglandin E1 (PGE1) on diabetic foot ulcer healing suggests possible benefits. However, good quality, large-scale confirmatory research is needed. (ABSTRACT TRUNCATED)

Administration, Topical↗
PubMed2004

Vitamin C for preventing and treating the common cold.

BACKGROUND: The role of oral vitamin C (ascorbic acid) in the prevention and treatment of the common cold has been a subject of controversy for at least sixty years. Public interest in the topic continues to be high and vitamin C continues to be widely sold and used as a preventive and therapeutic agent for this common ailment. OBJECTIVES: To discover whether oral vitamin C in doses of 200 mg or more daily, reduces the incidence, duration or severity of the common cold when used either as continuous prophylaxis or after the onset of cold symptoms. SEARCH STRATEGY: This updated review added to earlier searches, a full search of the following electronic databases: the Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June 2004); and EMBASE (1990 to June 2004). SELECTION CRITERIA: Papers were excluded if a dose less than 200 mg daily of vitamin C was used; if there was no placebo comparison; if methods of outcome assessment were inadequately described; and if the report did not record any of the three study outcomes (incidence, duration or severity) in sufficient detail to enter into the meta-analysis. Three criteria of study quality were assessed: Jadad scores, placebo distinguish-ability, and allocation concealment. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. 'Incidence' of colds during prophylaxis was assessed as the proportion of participants experiencing one or more colds during the study period. 'Duration' was the mean days of illness of cold episodes and 'severity' of these episodes was assessed by days confined indoors, off work or school. or by symptom severity scores. MAIN RESULTS: Twenty-nine trial comparisons involving 11,077 study participants contributed to the meta-analysis on the relative risk (RR) of developing a cold while taking prophylaxis. The pooled RR was 0.96 (95% CI 0.92 to 1.00). A subgroup of six trials that involved a total of 642 marathon runners, skiers, and soldiers on sub-arctic exercises reported a pooled RR of 0.50 (95%CI 0.38 to 0.66). Thirty comparisons that involved 9,676 respiratory episodes contributed to the meta-analysis on common cold duration during prophylaxis . A consistent benefit was observed, representing a reduction in cold duration of 8% (95% CI 3% to 13%) for adult participants and 13.5% (95% CI 5% to 21%) for child participants. Fifteen trial comparisons that involved 7,045 respiratory episodes contributed to the meta-analysis of severity of episodes experienced while on prophylaxis. The pooled results revealed a difference favouring those on vitamin C when days confined to home and off work or school were taken as a measure of severity (p = 0.02), and when restricting to studies which used symptom severity scores (p = 0.16), and for the both measures of severity combined (p = 0.004). Seven trial comparisons that involved 3,294 respiratory episodes contributed to the meta-analysis of cold duration during therapy with vitamin C that was initiated after the onset of cold symptoms, and no significant difference from placebo was seen. Four trial comparisons that involved 2,753 respiratory episodes, contributed to the meta-analysis of cold severity during therapy and no significant difference from placebo was seen.In laboratory studies, differing methods of artificial transmission of virus to vitamin C or placebo treated volunteers in residential experiments gave different results. Volunteers infected by nasal installation showed small or no benefit from vitamin C, whereas a group who were infected more naturally, reported less severe symptom severity scores (p = 0.04). REVIEWERS' CONCLUSIONS: The failure of vitamin C supplementation to reduce the incidence of colds in the normal population indicates that routine mega-dose prophylaxis is not rationally justified for community use. But evidence shows that it could be justified in persons exposed to brief periods of severe physical exercise and/or cold environments. Also, the consistent and statistically significant small benefits on duration and severity for those using regular vitamin C prophylaxis indicates that vitamin C plays some role in respiratory defence mechanisms. The trials in which vitamin C was introduced at the onset of colds as therapy did not show any benefit in doses up to 4 grams daily, but one large trial reported equivocal benefit from an 8 gram therapeutic dose at onset of symptoms.

Administration, Oral↗
PubMed2004

Delayed antibiotics for symptoms and complications of respiratory infections.

BACKGROUND: The use of antibiotics for upper respiratory tract infections is controversial. Any benefits have to be weighed against common adverse reactions (including rash, abdominal pain, diarrhoea and vomiting), cost and antibacterial resistance. There has been interest in ways to reduce antibiotic prescribing for acute respiratory infections. One is delaying the use of prescribed antibiotics by more than 48 hours for acute upper respiratory tract infections. Such methods have been shown to reduce prescribing. This review asks what effect this practice has on the clinical course of the illness. OBJECTIVES: To evaluate the clinical effect of delayed antibiotic use in acute upper respiratory tract infections compared to immediate use of antibiotics SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004) which includes the Acute Respiratory Infection Groups' specialised register; MEDLINE (January 1966 to January Week 1 2004), EMBASE (1990 to September 2003) and Current Contents (1998 to 2003). The search was carried out by an expert librarian. Abstracts of identified articles were used to determine which studies were trials. SELECTION CRITERIA: Randomised controlled trials involving patients of all ages defined as having acute otitis media, acute pharyngitis, sore throat, common cold, a viral upper respiratory tract infection, acute sinusitis, and acute bronchitis were included in which delayed antibiotics are compared to antibiotics used immediately. Delayed antibiotic use was defined as the use of or advice to use antibiotics more than 48 hours after the initial consultation. 'Immediate antibiotic use' was defined as the immediate use of oral antibiotics given at the initial consultation. Clinical outcomes measured included: the presence or absence of fever, cough, pain, duration and severity of illness, complications of the disease, adverse effects from the antibiotics. Trial quality was assessed independently by two reviewers who were blinded to the author, journal and results of each study. DATA COLLECTION AND ANALYSIS: Data was collected by two reviewers who were blinded to the author and journal. Data were analysed and reported using RevMan. MAIN RESULTS: Seven trials were eligible on the basis of design and all reported patient-centred outcomes. Methodological quality of included trials was generally high. There was no difference between immediate and delayed antibiotic groups for symptoms on day one and day seven. For most symptom measures there was no significant difference between the immediate and delayed antibiotic groups. Missing data and marked heterogeneity between study outcomes prevented pooling of results as a meta-analysis. Three studies out of six reporting fever, all involving patients with sore throat, indicated that there was more fever in the delayed antibiotic group. The remaining three studies showed no difference. There was no significant symptom difference for patients with cough or the common cold between the two intervention groups. Pain and malaise severity scores at day three significantly favoured the immediate antibiotic group in children with acute otitis media (Little 2001). In this study by Little 2001 of children with otitis media proxies for other malaise related outcomes were reported, including 'last day of crying' which favoured the immediate antibiotic group by approximately 16 hours (0.69 days; 95% CI 0.31 to 1.07). In the same study, just over half a spoon of paracetamol a day less was used in the immediate antibiotic group (0.59; 95% CI 0.25 to 0.93). There was no significant difference between the intervention groups for the adverse outcome of rash. Two studies reported the outcome of vomiting which was reduced in the immediate antibiotic group in children with suspected streptococcal pharyngitis in El-Daher 1991 but there was no difference in children with sore throat in Little 1997. Diarrhoea was reported by three studies of which two showed no difference Little 1997; Arroll 2002a while Little 2001 reported less diarrhoea in the delayed antibiotic group in children with otitis media. REVIEWERS' CONCLUSIONS: When considering treatment options for upper respiratory tract infections, the option of delayed antibiotics has been used in an attempt to reduce the use of antibiotic prescriptions. This review shows that for all symptom scores the evidence varies between trials. Most symptom outcomes show no difference between immediate and delayed antibiotic groups. Three of the six studies, all involving patients with sore throat, indicated that patients in the delayed antibiotic group had significantly more fever that their counterparts in the immediate antibiotic group. The other three showed no difference for the outcome of fever. There is evidence indicating that for children with otitis media, pain and malaise scores are worse in the delayed antibiotic group compared to the immediate antibiotic group. This price must be weighed up against the benefits of reduced antibiotic prescribing. Future randomised controlled trials of delaying antibiotics as an intervention should fully report symptoms as well as changes of prescription rates.

Anti-Bacterial Agents↗
PubMed2004

Over-the-counter medications for acute cough in children and adults in ambulatory settings.

BACKGROUND: Acute cough due to upper respiratory tract infection (URTI) is a common symptom. Many health practitioners recommend non-prescription over-the-counter (OTC) medicines as a first-line treatment for cough, but there is little evidence as to whether these drugs are effective. OBJECTIVES: To assess the effects of oral over-the-counter cough preparations for acute cough. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to June Week 3, 2004); EMBASE (January 1990 to March 2004); and the UK Department of Health National Research Register (December 2003, http://www.update-software.com/National/nrr-frame.html). We also searched personal collections of references and reference lists of articles. We wrote to study investigators and pharmaceutical companies for information on further published or unpublished studies. There were no constraints based on language or publication status. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral OTC cough preparations with placebo in children and adults suffering from acute cough in ambulatory settings. We considered all cough outcomes (such as frequency and severity, continuous and categorical data, using different ways of measurement). The second outcomes of interest were adverse effects. DATA COLLECTION AND ANALYSIS: Two investigators screened potentially relevant citations independently. Any differences at any stage of the review were resolved by discussion. We also extracted data and assessed the quality of studies independently. We contacted investigators for additional information and performed quantitative analysis when appropriate data were available. MAIN RESULTS: Twenty four trials (17 in adults, seven in children) involving 3,392 people (2,876 adults and 516 children) were included. RESULTS OF STUDIES IN ADULTS: 1. Antitussives: Six trials compared antitussives with placebo. Codeine was no more effective than placebo in reducing cough symptoms. Two studies favoured dextromethorphan over placebo, whereas a third did not show an effect. Moguisteine was no more effective than placebo apart from a reduction of cough in a subgroup of participants with more severe night cough. 2. Expectorants: Two trials compared guaifenesin with placebo. In the larger study, 75 per cent of participants taking guaifenesin stated that the medicine was helpful compared to 31 per cent in the control group. In the second study, both groups showed improvement with respect to cough frequency and severity, with no statistically significant differences between groups. 3. Mucolytics: One trial compared a mucolytic with placebo. Active treatment reduced cough frequency and symptom scores on day four and eight. 4. Antihistamine-decongestant combinations: Two studies compared antihistamine-decongestant combinations with placebo. Antihistamine-decongestants were significantly more effective than placebo in one of the studies, whereas the other did not show any difference between the study groups. 5. Other drug combinations: Three studies compared combinations of drugs other than antihistamine-decongestant with placebo. Two studies were effective in reducing cough symptoms, and one study showed relief at night but not during the day. 6. Antihistamines: Three trials compared antihistamines with placebo. Antihistamines were no more effective than placebo in relieving cough symptoms. RESULTS OF STUDIES IN CHILDREN: 1. Antitussives: Antitussives were no more effective than placebo (one study) 2. Expectorants: No studies using expectorants met our inclusion criteria. 3. Mucolytics: The results of one trial favoured active treatment over placebo from day four until day 10. 4. Antihistamine-decongestant combinations: Two studies showed no difference between antihistamine-decongestant combinations and placebo. 5. Other drug combinations: One trial tested two paediatric cough syrups. Compared to placebo, both preparations showed a 'satisfactory response' in 46 per cent and 56 per cent of children compared to 21 per cent of children in the placebo group. One study compared an antitussive/bronchodilator combination in children, which showed no difference between the treatment groups. 6. Antihistamines: In one trial that tested antihistamines active treatment was no more effective than placebo. REVIEWERS' CONCLUSIONS: There is no good evidence for or against the effectiveness of OTC medicines in acute cough. The results of this review have to be interpreted with caution due to differences in study designs, populations, interventions and outcomes between studies. The numbers of studies in each group were small, and studies often showed conflicting results. Effect sizes in many studies were unclear and it is questionable as to whether all of the positive results are clinically relevant. More evidence about the effectiveness of OTC cough preparations would be helpful, as identification of effective self-care treatments may help reduce the burden of days lost at work due to acute cough as well as the number of consultations in primary care. Identification of ineffective preparations could avoid costs for consumers and health care providers.

Acute Disease↗
PubMed2000

Inhaled nitric oxide for acute hypoxemic respiratory failure in children and adults.

OBJECTIVES: To determine the effect of iNO, compared with inhaled placebo, on outcome in AHRF in children and/or adults. SEARCH STRATEGY: Randomised controlled trials (RCT's) were identified from electronic databases; MEDLINE, EMBASE, the Cochrane Library, and CINAHL, as well as from bibliographies of retrieved articles. Relevant journals and conference proceedings were hand searched and authors published in this field were contacted for knowledge of unpublished ongoing trials. SELECTION CRITERIA: RCT's comparing iNO with maximal conventional therapy and inhaled placebo, for AHRF in either children or adults. DATA COLLECTION AND ANALYSIS: Data were extracted and the analyses performed independently by two reviewers. All 5 authors were contacted for missing data. Qualitative assessment of each trial was made according to methodology described by Schulz (Schulz 1995), and analyses according to statistical methods in Review Manager MetaView 3.1. The fixed effect model was applied. Where possible, sub-group analyses were performed to assess the impact of iNO in varied doses. MAIN RESULTS: Five RCT's were evaluated, assessing 535 patients with AHRF. Inhaled nitric oxide made no impact on mortality in trials without cross-over (RR 0.98, 95%CI 0.66, 1.44), or with cross-over of treatment failures to open-label iNO (RR 1.22, 95%CI 0.65, 2.29). Published evidence from one study demonstrated that iNO resulted in a transient improvement in oxygenation in the first 24 hours of treatment: the oxygenation index (OI) showed a mean difference of -3 [95% CI -5.354, -0.646], and PaO2/FiO2 ratio, a mean difference of 35 [95% CI 20.236, 49.764]. Limited data demonstrated no difference in ventilator-free days between treatment and placebo groups, and no specific dose of iNO was significantly advantageous over another. Other clinical indicators of effectiveness, such as duration of hospital and intensive care stay, were inconsistently reported. There were no complications reported to be directly attributable to this treatment. REVIEWER'S CONCLUSIONS: From the data provided to date, iNO had no effect on mortality and only transiently improved oxygenation in AHRF in children and/or adults. There was a lack of data to assess other end points. The long term adverse effects of this drug are not known, as no long term follow-up of trial participants has been reported. If further trials comparing iNO with an inhaled placebo are to proceed, they should be stratified for primary disease and must specifically evaluate clinically relevant outcomes, before any benefit of iNO in AHRF can be excluded.

Acute Disease↗