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Topical treatments for seasonal allergic conjunctivitis: systematic review and meta-analysis of efficacy and effectiveness.

BACKGROUND: Evidence for the effectiveness of topical treatments, in providing symptomatic relief from ocular allergy, remains uncertain. AIMS: To assess the effectiveness and relative efficacy of topical treatments for the management of seasonal allergic conjunctivitis. DESIGN OF STUDY: A systematic review and meta-analysis. SETTING: A literature search of the Cochrane Library, Medline, and EMBASE bibliographic databases. METHOD: Double-masked randomised controlled trials were identified, that compared the use of topical mast cell stabilisers (sodium cromoglycate, nedocromil, lodoxamide) with placebo, topical antihistamines with placebo, and topical mast cell stabilisers with topical antihistamines. RESULTS: A meta-analysis of six trials showed that patients using sodium cromoglycate were 17 times (95% confidence interval [CI] = 4 to 78) more likely to perceive benefit compared with those using a placebo, although this estimate may be partially influenced by publication bias. Five trials indicated that those patients using nedocromil were 1.8 times (95% CI = 1.3 to 2.6) more likely to perceive their allergy to be moderately or totally controlled than those using a placebo. Four trials showed that those using antihistamines were 1.3 times (95% CI = 0.8 to 2.2) more likely to perceive a 'good' treatment effect than those using mast cell stabilisers, although this beneficial effect was not statistically significant. Limited evidence suggests that antihistamines might have a faster therapeutic effect compared to mast cell stabilisers. CONCLUSION: Overall, these findings confirm the benefit of topical mast cell stabilisers and antihistamines over placebo for the treatment of allergic conjunctivitis. There is, however, insufficient evidence to recommend the use of one type of medication over another. Treatment preferences should therefore be based on convenience of use (with reduced frequency of instillation for some preparations), patient preference, and costs, especially as important side effects were not reported with any medication.

Administration, Topical↗

Nebulized racemic epinephrine for extubation of newborn infants.

BACKGROUND: Following a period of mechanical ventilation, post-extubation upper airway obstruction can occur in newborn infants, especially after prolonged, traumatic or multiple intubations. The subsequent increase in upper airway resistance may lead to respiratory insufficiency and failure of extubation. The vasoconstrictive properties of epinephrine, and its proven efficacy in the treatment of croup in infants, has led to the routine use of inhaled nebulised epinephrine immediately post-extubation in some neonatal units. It is also recommended for neonates with post-extubation tracheal obstruction and stridor in neonatal and respiratory textbooks and reviews. OBJECTIVES: The primary objective was to assess whether nebulised epinephrine administered immediately after extubation in neonates weaned from IPPV decreases the need for subsequent additional respiratory support. SEARCH STRATEGY: Searches were made of Medline (MeSH search terms 'epinephrine' and 'exp infant, newborn'), the Oxford Database of Perinatal trials, expert informants and journal hand searching mainly in the English language, expert informant searches in the Japanese language by Prof. Ogawa, previous reviews including cross references, abstracts, and conference and symposia proceedings. SELECTION CRITERIA: All randomised and quasi-randomised control trials in which nebulised epinephrine was compared with placebo immediately post-extubation in newborn infants who have been weaned from IPPV and extubated, with regard to clinically important outcomes (i.e. need for additional respiratory support, increase in oxygen requirement, respiratory distress, stridor or the occurrence of side effects). DATA COLLECTION AND ANALYSIS: No studies met our criteria for inclusion in this review. MAIN RESULTS: No studies were identified which looked at the effect of inhaled nebulised epinephrine on clinically important outcomes in infants being extubated. REVIEWER'S CONCLUSIONS IMPLICATIONS FOR PRACTICE: There is no evidence either supporting or refuting the use of inhaled nebulised racemic epinephrine in newborn infants. IMPLICATIONS FOR RESEARCH: randomised controlled trials are needed comparing inhaled nebulised racemic epinephrine with placebo in neonates post-extubation. This should be looked at both as a routine treatment post-extubation and as specific treatment for post-extubation upper airway obstruction. Study populations should include the group of infants at highest risk for upper airway obstruction from mucosal swelling because of their small glottic and sub-glottic diameters (ie those infants with birthweights less than 1000 grams).

Administration, Inhalation↗

Short versus standard duration oral antibiotic therapy for acute urinary tract infection in children.

BACKGROUND: The optimal duration of oral antibiotic therapy for urinary tract infection (UTI) in children has not been determined. A number of studies have compared single dose therapy to standard therapy for UTI, with mixed results. A course of antibiotics longer than a single dose but shorter than the usual 7-10 days might decrease the relapse rate and still provide some of the benefits of a shortened course of antibiotics. OBJECTIVES: The objective of this review was to assess the benefits and harms of short-course (2-4 days) compared to standard duration (7-14 days) oral antibiotic treatment for acute UTI in children. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002) MEDLINE (1966 - September 2002) and EMBASE (1988 -September 2002) without language restriction. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing short-term (2-4 days) with standard (7-14 days) oral antibiotic therapy were selected if they studied children aged three months to 18 years with culture proven UTI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (95% CI). MAIN RESULTS: Ten trials were identified in which 652 children with lower tract UTI were evaluated. There was no significant difference in the frequency of positive urine cultures between the short (2-4 days) and standard duration oral antibiotic therapy (7-14 days) for UTI in children at 0-10 days after treatment (eight studies: RR 1.06; 95% CI 0.64 to 1.76) and at one to 15 months after treatment (10 studies: RR 0.95; 95% CI 0.70 to 1.29). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (one study: RR 0.57, 95% CI 0.32 to 1.01) or in recurrent UTI (three studies: RR 0.39, 95% CI 0.12 to 1.29). REVIEWER'S CONCLUSIONS: A 2-4 day course of oral antibiotics appears to be as effective as 7-14 days in eradicating lower tract UTI in children.

Acute Disease↗

[A meta-analysis of treatment of infantile diarrhea with bifid triple viable bacterial tablet].

OBJECTIVE: To assess the efficacy and safety of bifid triple viable bacterial tablet in treatment of infantile diarrhea. METHODS: According to the requirements of Cochrane systematic review, a thorough literature search was performed among Chinese Digital Hospital Library (www.chkd.cnki.net) and Chinese Biomedical Literature Disk Database (CBMdisk). A meta analysis was performed on a total of 1326 patients involved in 12 papers which met the inclusion criteria. RESULTS: Publication bias analysis showed that the funnel plot was symmetrical. Test for heterogeneity showed that the groups treated with bifid triple viable bacterial tablet and antibiotics or anti-viral agents or placebo control had clinical homogeneity and statistical homogeneity (P = 0.66, 0.67, 0.85, respectively, I(2) = 0%), which allowed to use fixed effect model analysis. The bifid triple viable bacterial tablet and Smecta did not have statistical homogeneity (P = 0.02, I(2) = 70.9%), therefore random effect model analysis was applied. Incorporation analysis showed that in comparison of the bifid triple viable bacterial tablet versus antibiotics or anti-viral agents or placebo control, the odds ratios were 5.34, 4.74 and 6.43, respectively, and 95% CIs were [2.81, 10.16], [2.47, 9.09], and [2.61, 15.83], on test for overall effect, Z = 5.11, 4.67 and 4.04, P < 0.00001. In the forest plot the 95% CI horizontal line of incorporation odds ratio droped to the right side of the vertical line indicating the border of effectiveness. However, no statistically significant difference was found between bifid triple viable bacterial tablet and Smecta. CONCLUSION: The clinical evidences available so far indicated that treatment of infantile diarrhea with bifid triple viable bacterial tablet is safe and effective although rigorously designed large sample size randomized double blind clinical trials are required to further demonstrate and support the conclusion.

Administration, Oral↗

Opioid antagonists for alcohol dependence.

BACKGROUND: The benefits of selective serotonin reuptake inhibitors, disulfiram, and lithium have not been clear for people with alcohol dependence. While the results of many studies have suggested that opioid agonists increase alcohol consumption, others have shown that mu-opioid antagonists and partial agonists reduce alcohol consumption. The results from animal studies suggest that these agents may prevent the reinforcing effects of alcohol consumption. Based on the results of those animal studies, some opioid antagonists, such as, naltrexone, nalmefene, have been studied for their benefits in treating alcohol dependence. OBJECTIVES: To determine the effectiveness of opioid antagonists in attenuating or preventing the recommencement of alcohol consumption in patients with alcohol dependence in comparison to placebo, other medications and psychosocial treatments. In addition, discontinuation rate, death, patient satisfaction, functioning, health-related quality of life and economic outcomes were also evaluated. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE, CINAHL and Cochrane Controlled Trials Register were undertaken. Du Pont Pharmaceutical and Ivax Corporation were contacted for information regarding unpublished trials. The reference lists of the obtained papers were also examined. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) and clinical control trials (CCTs) were included. Participants were people with alcohol dependence, diagnosed by any set of criteria, except alcohol dependence who were currently abstinent. Naltrexone (NTX), nalmefene (NMF) and other opioid antagonists with/without other biological or psychosocial treatments were examined. A variety of clinical outcomes, for example alcohol consumption, duration of abstinence, were considered. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated and extracted the data independently. The dichotomous data were extracted on an intention-to-treat basis in which the dropouts were assigned as participants with the worst outcomes. The Peto Odds Ratio with the 95% confidence interval was used to assess the dichotomous data. Weighted Mean Difference with 95% confidence interval was used to assess the continuous data. MAIN RESULTS: The short-term (< 3 months) benefits of NTX were shown in three respects, which were number of patients who return to drinking, percentage or number of drinking days and the number of standard drinks of alcohol. However, 6 months after the completion of 12-week NTX treatment, the benefit of decreasing the number of patients who return to drinking were lost. The short-term evidence from a small sample-size study suggested that disulfiram was more effective than NTX in the respects of number of abstinent days, percentage or number of drinking days and number of standard drinks of alcohol. The evidence from another small sample-size study also suggested that NTX plus an aversive agent was superior to an aversive agent alone in the respect of number of patients who return to drinking in short-, medium-, and long-term treatment. From two short-term and small sample-size studies, the benefit of NMF was shown only in the respect of number of patients who return to drinking. REVIEWER'S CONCLUSIONS: Due to the limited evidence, the following conclusions should be viewed as tentative. NTX has some benefits for patients with alcohol dependence, but patients' adherence to treatment should be of concern. Psychosocial treatments should be concurrently given with NTX. The optimal duration of NTX treatment is not yet known. Although NTX is available for treating alcohol dependence in many countries, in the respect of cost-effectiveness, disulfiram should still remain as an alternative. Due to the dearth of evidence, at present, the combination of NTX and disulfiram or NMF alone should not be used in everyday clinical practice. Randomised, double-blind, placebo-controlled trials of NTX treatment in patients with alcohol dependence

Alcoholism↗

Mass psychogenic illness following oral cholera immunization in Ca Mau City, Vietnam.

INTRODUCTION: Targeted cholera immunization of high-risk populations in Vietnam is conducted based on routine surveillance data. Following mass immunization of schoolchildren in Ca Mau City using an oral bivalent killed cholera vaccine, adverse reactions were noted. METHODS: Salient data were collected in a systematic fashion including the review of medical records; interview of the school principal, teachers, students, parents and doctors; and review of the storage and handling of the vaccine. FINDINGS: On 18 December 2001, 234 children at a primary school in Ca Mau City received the cholera vaccine. Within 1h of immunization, three children in one of the classrooms complained of trembling, nausea and headache and were brought to the library and soon other children followed. Out of 234, 97 (42%) pupils were affected and brought to the Municipal Health Center or Ca Mau Provincial Hospital. Those who were affected were younger (mean age=9.6 years; 95% CI=9.4-9.7) compared to those who were not affected (mean age=10 years; 95% CI=9.7-10.3; t-test=-2.4; P-value=0.02). The proportion of affected females among those who had received the vaccine (49/114 or 43%) was similar to the proportion in males (48/120 or 40%; RR=1.07; 95% CI=0.79-1.46). The most frequent presenting complaint was cold extremities (60%) followed by headache (27%). All affected children recovered and were discharged in a few hours. None reported any sequelae or relapse. Once the situation was recognized, the cholera immunization campaign was continued. Laboratory tests of vaccine samples from the same batch detected no abnormality or contaminating agent. DISCUSSION: The findings suggest that the children at primary school number 1 suffered from a mass psychogenic illness. This incident was unusual in that a similar number of boys and girls were affected, in contrast to the frequently reported preponderance of female cases. Furthermore the underlying cause was very quickly diagnosed, medical interventions were kept to a minimum, and no relapse was observed. Future vaccination campaigns have to assure that the families are informed in advance.

Administration, Oral↗

Local oestrogen for vaginal atrophy in postmenopausal women.

BACKGROUND: Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the estradiol releasing ring). OBJECTIVES: The objective of this review is to compare the effectiveness, safety and acceptability of oestrogenic preparations for women who suffer from vaginal atrophy. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group register of trials (searched January 2003), The Cochrane Library (Issue 2, 2003), MEDLINE (1966-January 2003), EMBASE (1980-January 2003), Current Contents (1993-January 2003), Biological Abstracts (1969-2002), Social Sciences Index (1980-January 2003), PsycINFO (1972-February 2003), CINAHL (1982-January 2003) and reference list of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for the treatment of symptoms resulting from vaginal atrophy or vaginitis. DATA COLLECTION AND ANALYSIS: Twenty nine trials were identified, of these 13 were excluded. Trials were assessed for quality and two reviewers extracted data independently. Ratios for dichotomous and means for continuous outcomes were estimated. Outcomes analysed were included under the headings of efficacy, safety and acceptability. MAIN RESULTS: Sixteen trials with 2129 women were included in this review. The overall quality of the studies was good, although not all trials measured the same outcomes. All trials measured efficacy with various outcome measures. When comparing efficacy of oestrogenic preparations (in the form of creams, pessaries, tablets and the estradiol releasing vaginal ring) with each other in relieving the symptoms of vaginal atrophy, results indicated significant differences favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and six looked at adverse effects. One trial showed significant adverse effects of cream (conjugated equine oestrogen) when compared to tablets (estradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by progestagen challenge test in the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (estradiol). Nine studies compared acceptability to the participants by comparing comfort of product, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the estradiol releasing vaginal ring. REVIEWER'S CONCLUSIONS: Creams, pessaries, tablets and the estradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects noted following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the estradiol releasing vaginal ring for ease of use, comfort of product and overall satisfaction.

Administration, Intravaginal↗

Systematic review of randomized controlled trials of misoprostol to prevent postpartum hemorrhage.

OBJECTIVE: To assess the effects of prophylactic misoprostol use in the third stage of labor compared with injectable uterotonics or placebo or no treatment. DATA SOURCES: The Cochrane Pregnancy and Childbirth Group trials register; the Cochrane Library, including databases such as the database of systematic reviews and the Cochrane Controlled Trials Register; and MEDLINE were searched. Researchers in the field were also contacted. The date of the latest search was March 1, 2002. METHODS OF STUDY SELECTION: Randomized trials comparing misoprostol with injectable oxytocin or oxytocin-ergot preparations to prevent postpartum hemorrhage or placebo/no treatment as active management of the third stage of labor were eligible for inclusion. Eligibility and trial quality were assessed following selected criteria. Data were extracted and analyzed using RevMan software. TABULATION, INTEGRATION, AND RESULTS: Sixteen randomized trials with a total of 28,138 women were considered. Data were available for 27,498 women. Oral misoprostol (600 microg) is less effective than injectable uterotonics in reducing blood loss at least 1000 mL (relative risk [RR] 1.36, 95% confidence interval [CI] 1.17, 1.58) and increases the use of additional uterotonics. Shivering and pyrexia (temperature greater than 38C) are the main side effects of misoprostol and are dose related. Compared with injectable uterotonics, the RR of "any shivering" with misoprostol (600 microg) is 3.27 (95% CI 3.01, 3.56) and pyrexia is 6.96 (95% CI 5.65, 8.57). The RR of blood loss of 500 mL or more is 1.11 (95% CI 0.87, 1.43) and the RR of use of additional uterotonics is 1.80 (1.13, 2.85) in the three trials (1441 women) comparing rectal misoprostol (400 microg) with injectable uterotonics. CONCLUSION: Injectable oxytocin or oxytocin-ergot preparations are more effective than misoprostol as part of the active management of the third stage of labor.

Administration, Oral↗

Oral antibiotics versus parenteral antibiotics for severe pneumonia in children.

BACKGROUND: Acute respiratory infection (ARI) is one of the leading causes of morbidity and mortality in children under five years of age in developing countries. When hospitalisation is required, the usual practice includes administering parenteral antibiotics if a bacterial infection is suspected. This has disadvantages as it causes pain and discomfort to the children, which may lead to treatment refusal or reduced compliance. It is also associated with needle-related complications. In some settings this equipment is in short supply or unavailable necessitating transfer of the child, which increases risks and healthcare costs. OBJECTIVES: To determine the equivalence in effectiveness and safety of oral antibiotic compared to parenteral antibiotic therapies in the treatment of severe pneumonia in children between three months and five years of age. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2005); MEDLINE (January 1966 to July 2005); EMBASE (January 1990 to July 2005) and LILACS (February 2005). SELECTION CRITERIA: The review included published or unpublished randomised controlled trials (RCTs) and quasi-RCTs comparing any oral antibiotic therapy with any parenteral antibiotic therapy for the treatment of severe pneumonia in children from three months to five years of age. DATA COLLECTION AND ANALYSIS: The search yielded more than 1300 titles. Only three studies met all criteria for eligibility. One of the identified trials is yet to publish its results. We did not perform a meta-analysis because of clinical heterogeneity of therapies compared in the included trials. MAIN RESULTS: Campbell 1988 compared oral co-trimoxazole versus intramuscular procaine penicillin followed by oral ampicillin in 134 children. At the seventh day of follow up, treatment failure occurred in 6/66 (9.1%) in the oral co-trimoxazole group and 7/68 (10.2%) in the combined-treatment group. The risk difference was -0.01% (95% confidence interval (CI) -0.11 to 0.09). The APPIS Group 2004 evaluated 1702 patients comparing oral amoxicillin versus intravenous penicillin for two days followed by oral amoxicillin. After 48 hours, treatment failure occurred in 161/845 (19%) in the amoxicillin group and 167/857 (19%) in the parenteral penicillin group. The risk difference was -0.4% (95% CI -4.2 to 3.3). The authors reported similar recovery in both groups at 5 and 14 days. AUTHORS' CONCLUSIONS: Oral therapy appears to be an effective and safe alternative to parenteral antibiotics in hospitalised children with severe pneumonia who do not have any serious signs or symptoms.

Administration, Oral↗

Rectal analgesia for pain from perineal trauma following childbirth.

BACKGROUND: Perineal pain from a tear and/or surgical cut (episiotomy) is a common problem following vaginal birth. Strategies to reduce perineal trauma and the appropriate repair of any perineal damage sustained are important for avoiding and alleviating pain. Where pain is present, numerous treatments are used in clinical practice, such as local anaesthetics, oral analgesics, therapeutic ultrasound, antiseptics and non-pharmacological applications such as ice packs and baths. This review assesses the evidence for using rectal analgesia for pain relief following perineal trauma. OBJECTIVES: To assess the effectiveness of analgesic rectal suppositories for pain from perineal trauma following childbirth. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2002), CENTRAL (The Cochrane Library, Issue 2, 2002), CINAHL (May 2002) and MIDIRS (May 2002). SELECTION CRITERIA: Randomised controlled trials comparing analgesic rectal suppositories with placebo or alternative treatment for the relief of perineal pain. DATA COLLECTION AND ANALYSIS: Two reviewers assessed trial quality and extracted data independently. MAIN RESULTS: Three trials involving 249 women met the inclusion criteria. Only two of the trials identified for inclusion in this review had data that could be entered in a meta-analysis, with the third not providing data in a useable format. Women were less likely to experience pain at or close to 24 hours after birth if they received non-steroidal anti-inflammatory drugs (NSAID) suppositories compared with placebo (relative risk (RR) 0.37, 95% confidence interval (CI) 0.10 to 1.38, 2 trials, 150 women). Women in the NSAID suppositories group compared with women in the placebo group required less additional analgesia in the first 24 hours after birth (RR 0.31, 95% CI 0.17 to 0.54, 1 trial, 89 women) and this effect was still evident at 48 hours postpartum (RR 0.63, 95% CI 0.45 to 0.89, 1 trial, 89 women). No information was available on pain experienced more than 72 hours after birth or other outcomes of importance to women such as the impact on daily activities, resumption of sexual intercourse and the impact on the mother-baby relationship. REVIEWER'S CONCLUSIONS: NSAID rectal suppositories are associated with less pain up to 24 hours after birth, and less additional analgesia is required. More research is required regarding long-term effects and maternal satisfaction with the treatment.

Administration, Rectal↗

Depot pipothiazine palmitate and undeclynate for schizophrenia.

BACKGROUND: Anti-psychotic drugs are usually given orally but compliance with medication given by this route may be difficult to quantify. The development of depot injections in the 1960s gave rise to extensive use of depots as a means of long-term maintenance treatment. Pipothiazine palmitate is a depot from the phenothiazine family of antipsychotic drugs. OBJECTIVES: To assess the effects of depot pipothiazine palmitate and undeclynate versus placebo, oral anti-psychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes. SEARCH STRATEGY: Relevant trials were identified by searching Biological Abstracts (1982-1998), Cochrane Library (Issue 2, 1998), Cochrane Schizophrenia Group's Register (June 1998), EMBASE (1980-1998), MEDLINE (1966-1998) and PsycLIT (1974-1998). References of all identified trials were also inspected for more studies and industry contacted. SELECTION CRITERIA: All clinical randomised trials focusing on people with schizophrenia where depot pipothiazine palmitate and undeclynate, oral anti-psychotics or other depot preparations were compared. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, quality rated and data extracted. For dichotomous data Peto odds ratios (OR) with the 95% confidence intervals (CI) were estimated. Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data were summated using the weighted mean difference (WMD). Scale data were presented only for those tools that had attained pre-specified levels of quality. MAIN RESULTS: Fourteen studies were included. When pipothiazine palmitate was compared to 'standard' oral antipsychotics no differences were found for outcomes of mental state, study attrition, behaviour and adverse effects (total randomised = 166). Pipothiazine palmitate was compared to other depot preparations in nine studies (n=455). Again no differences were identified for outcomes of global improvement, mental state, study attrition, behaviour and adverse effects. REVIEWER'S CONCLUSIONS: Although well-conducted and reported randomised trials are still needed to inform practice (no trial data exists reporting hospital and services outcomes, satisfaction with care and economics) pipothiazine palmitate is a viable choice for clinician and recipient of care. Data suggests it is not different to other depot antipsychotics.

Antipsychotic Agents↗

Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome. CONCLUSIONS: The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗

Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states: gene structure and 5'-flanking sequence.

The mRNA level of the catalytic subunit of rat liver glucose-6-phosphatase (Glu-6-Pase) was regulated by hormones commensurate with activity changes in vivo. Insulin exerts a dominant negative effect on the mRNA levels of Glu-6-Pase. Both mRNA levels and activities of the enzyme are low in the fed and refed state where insulin levels are elevated. Insulin administration to diabetic rats also decreases levels of mRNA and Glu-6-Pase activity. Insulin at a concentration of 1 nmol/l completely overcomes the stimulatory effect of glucocorticoids on Glu-6-Pase message levels in FAO hepatoma cells. The stimulatory response to glucocorticoid in FAO cells is biphasic, with maxima seen at 3 and 18 h after hormone addition (respectively 1.6- and 3.3-fold). 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) causes a fourfold increase in Glu-6-Pase mRNA at 3 h in FAO cells. The gene of rat liver Glu-6-Pase is 13 kilobases in length and comprised of 5 exons. The exon-intron structure is completely conserved when compared with the mouse and human genes. A 0.5-kb 3'-untranslated region, which is present in rat and mouse liver Glu-6-Pase cDNA, is absent in the Glu-6-Pase gene reported here, indicating the possible duplication of either the terminal fifth exon or the entire gene. The promoter region contains a consensus core CCAAT element at position -207 and a TATAAA at position -31. Several possible response elements have been identified in the 5'-flanking region (from a HindIII site at position -1641). A consensus glucocorticoid response element is located at base pair -1552, a 9/10 match of the insulin response sequence is located at position -1449, and a 7/8 match of the cAMP response element is located at position -164.

Amino Acid Sequence↗

Amantadine and rimantadine for influenza A in adults.

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they 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 efficacy, 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 3, 2005), MEDLINE (2003 to August Week 4, 2005), EMBASE (October 2003 to July 2005) and reference lists of articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control medication or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prophylaxis (prevention) trials the numbers of participants with clinical influenza (influenza-like-illness or ILI) or with confirmed influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever, length of hospital stay and 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 1.2). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prophylaxis 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. Neither drug affected the rate of viral shedding from the nose and the course of asymptomatic influenza. AUTHORS' CONCLUSIONS: Amantadine and rimantadine have comparable efficacy and effectiveness in relieving or treating symptoms of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine. The effectiveness of both drugs in interrupting transmission is probably low. Routine use of both drugs should be discouraged and both drugs should only be used when all other measures fail.

Adult↗

Local oestrogen for vaginal atrophy in postmenopausal women.

BACKGROUND: Vaginal atrophy is a frequent complaint of postmenopausal women; symptoms include vaginal dryness, itching, discomfort and painful intercourse. Systemic treatment for these symptoms in the form of oral hormone replacement therapy is not always necessary. An alternative choice is oestrogenic preparations administered vaginally (in the form of creams, pessaries, tablets and the oestradiol-releasing ring). OBJECTIVES: The objective of this review was to compare the effectiveness, safety and acceptability of oestrogenic preparations for women who suffer from vaginal atrophy. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Register of trials (searched January 2006), The Cochrane Library (2006,Issue 2), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), Current Contents (1993 to January 2006, Biological Abstracts (1969 to 2006), Social Sciences Index (1980 to January 2006), PsycINFO (1972 to February 2006), CINAHL (1982 to January 2006) and reference list of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: The inclusion criteria were randomised comparisons of oestrogenic preparations administered intravaginally in postmenopausal women for the treatment of symptoms resulting from vaginal atrophy or vaginitis. DATA COLLECTION AND ANALYSIS: Thirty-seven trials were identified: of these 18 were excluded. Included trials were assessed for quality and two reviewer authors extracted data independently. The ratios for dichotomous outcomes and means for continuous outcomes were calculated. The outcomes analysed were categorised under the headings of: efficacy, safety and acceptability. MAIN RESULTS: Nineteen trials with 4162 women were included in this review. The overall quality of the studies was good, although not all trials measured the same outcomes. All trials measured efficacy, with various outcome measures. When comparing the efficacy of different oestrogenic preparations (in the form of creams, pessaries, tablets and the oestradiol-releasing vaginal ring) in relieving the symptoms of vaginal atrophy, results indicated significant findings favouring the cream, ring, and tablets when compared to placebo and non-hormonal gel. Fourteen trials compared safety. Four looked at hyperplasia, four looked at endometrial overstimulation and seven looked at adverse effects. One trial showed significant adverse effects of the cream (conjugated equine oestrogen) when compared to tablets (oestradiol) which included uterine bleeding, breast pain and perineal pain (1 RCT; OR 0.18, 95% CI 0.07 to 0.50). Two trials showed significant endometrial overstimulation as evaluated by a progestagen challenge test with the cream (conjugated equine oestrogen) group when compared to the ring (OR 0.29, 95% CI 0.11 to 0.78). Although not statistically significant there was a 2% incidence of simple hyperplasia in the ring group when compared to the cream (conjugated equine oestrogen) and 4% incidence of hyperplasia (one simple, one complex) in the cream group (conjugated equine oestrogen) when compared to the tablet (oestradiol). Eleven studies compared acceptability to the participants by comparing: comfort of product use, ease of use, overall product rating, delivery system and satisfaction. Results showed a significant preference for the oestradiol-releasing vaginal ring. AUTHORS' CONCLUSIONS: Creams, pessaries, tablets and the oestradiol vaginal ring appeared to be equally effective for the symptoms of vaginal atrophy. One trial found significant side effects following cream (conjugated equine oestrogen) administration when compared to tablets causing uterine bleeding, breast pain and perineal pain. Another trial found significant endometrial overstimulation following use of the cream (conjugated equine oestrogen) when compared to the ring. As a treatment choice women appeared to favour the oestradiol-releasing vaginal ring for ease of use, comfort of product and overall satisfaction.

Administration, Intravaginal↗

Duration of intrapartum prophylaxis for neonatal group B streptococcal disease: a systematic review.

OBJECTIVE: To examine published evidence regarding duration of intrapartum antibiotic prophylaxis administered to pregnant women colonized with group B Streptococcus (GBS) to reduce infant colonization with GBS and to prevent early-onset GBS sepsis. DATA SOURCES: A search was conducted in The Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2006), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), CINAHL (1982 to January 2006), and in protocols and guidelines of the Centers for Disease Control and Prevention, American Academy of Pediatrics, and American College of Obstetrics and Gynecology. METHODS OF STUDY SELECTION: All randomized controlled trials and observational studies in which duration of intrapartum antibiotic prophylaxis is reported relative to subsequent neonatal GBS colonization or sepsis were considered. Case series and study designs using historical cohorts or controls for comparison were excluded. TABULATION, INTEGRATION, AND RESULTS: Three prospective cohort studies and one case-control study met inclusion criteria. Heterogeneity of study design and assembly of cohorts precluded meta-analysis. A systematic review of the individual studies was performed. All studies were rated as fair or poor validity with regard to their ability to evaluate duration of intrapartum prophylaxis and transmission of GBS to the newborn. All 4 studies were largely composed of women with existing risk factors for GBS disease of the newborn. One study supported more than 1 hour of prophylaxis, two studies supported more than 2 hours of prophylaxis, and one was inconclusive. CONCLUSION: Despite unequivocal clinical guidelines recommending at least 4 hours of intrapartum antibiotic prophylaxis, there are no well-designed studies examining duration of intrapartum antibiotic prophylaxis for prevention of early-onset GBS disease of the newborn. We recommend continuing to initiate intrapartum prophylaxis according to the American College of Obstetricians and Gynecologists guidelines; however, the transmission of GBS to neonates exposed to less than 4 hours of intrapartum prophylaxis and their subsequent management require further study.

Antibiotic Prophylaxis↗

Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis.

BACKGROUND: Acute bronchitis leading to ongoing exacerbations is a serious condition predisposed to by viruses, bacteria or environmental factors. It can be fatal. Antibiotic therapy is not particularly useful. An oral Haemophilus influenzae vaccine has been developed. OBJECTIVES: To assess the effects of an oral, monobacterial whole-cell, killed, nontypeable H. influenzae vaccine in protecting against recurrent acute episodes in chronic bronchitis. SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to January Week 4 2006), EMBASE (1990 to September 2005) and ISI Current Contents (2004 to May 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of the H. influenzae vaccine on patients with recurrent acute exacerbations of chronic bronchitis were included when there was overt matching of the vaccine and placebo groups on clinical grounds. DATA COLLECTION AND ANALYSIS: Three authors extracted data and assessed trial quality independently from original records and publications for incidence and severity of bronchitis episodes and carriage rate of nontypeable H. influenzae measured in the upper respiratory tract every three months following vaccination. MAIN RESULTS: Six trials were included in the study with a total of 440 participants. The vaccine reduced the incidence of bronchitic episodes at three months after vaccination (rate ratio is 0.69; 95% CI 0.41 to 1.14) and at six months after vaccination (rate ratio 0.82; 95% CI 0.62 to 1.09). If these results been statistically significant, they would have represented a reduction in acute bronchitic attacks for vaccinated individuals of 31% at three months, and 18% at six. The effect had disappeared by nine months. The severity of exacerbations in the treatment group, as measured by requirement to prescribe antibiotics, was likewise reduced by 58% at three months (Peto odds ratio = 0.42; 95% CI 0.16 to 1.13), and by 65% at six months (Peto odds ratio = 0.35; 95% CI 0.16 to 0.75). AUTHORS' CONCLUSIONS: Vaccinating patients with recurrent acute exacerbations of chronic bronchitis in the autumn may reduce the number and severity of exacerbations over the following winter. A large clinical trial is needed.

Administration, Oral↗

Interventions to enhance patient adherence to medication prescriptions: scientific review.

CONTEXT: Low adherence with prescribed treatments is ubiquitous and undermines treatment benefits. OBJECTIVE: To systematically review published randomized controlled trials (RCTs) of interventions to assist patients' adherence to prescribed medications. DATA SOURCES: A search of MEDLINE, CINAHL, PSYCHLIT, SOCIOFILE, IPA, EMBASE, The Cochrane Library databases, and bibliographies was performed for records from 1967 through August 2001 to identify relevant articles of all RCTs of interventions intended to improve adherence to self-administered medications. STUDY SELECTION AND DATA EXTRACTION: Studies were included if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications for a medical or psychiatric disorder; both adherence and treatment outcome were measured; follow-up of at least 80% of each study group was reported; and the duration of follow-up for studies with positive initial findings was at least 6 months. Information on study design features, interventions, controls, and findings (adherence rates and patient outcomes) were extracted for each article. DATA SYNTHESIS: Studies were too disparate to warrant meta-analysis. Forty-nine percent of the interventions tested (19 of 39 in 33 studies) were associated with statistically significant increases in medication adherence and only 17 reported statistically significant improvements in treatment outcomes. Almost all the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, counseling, reminders, self-monitoring, reinforcement, family therapy, and other forms of additional supervision or attention. Even the most effective interventions had modest effects. CONCLUSIONS: Current methods of improving medication adherence for chronic health problems are mostly complex, labor-intensive, and not predictably effective. The full benefits of medications cannot be realized at currently achievable levels of adherence; therefore, more studies of innovative approaches to assist patients to follow prescriptions for medications are needed.

Acute Disease↗