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PubMed2005

Metformin monotherapy for type 2 diabetes mellitus.

BACKGROUND: Metformin is an anti-hyperglycaemic agent used for the treatment of type 2 diabetes mellitus. Type 2 diabetes may present long-term complications: micro- (retinopathy, nephropathy and neuropathy) and macrovascular (stroke, myocardial infarction and peripheral vascular disease). Two meta-analyses have been published before, although only secondary outcomes were assessed. OBJECTIVES: To assess the effects of metformin monotherapy on mortality, morbidity, quality of life, glycaemic control, body weight, lipid levels, blood pressure, insulinaemia, and albuminuria in patients with type 2 diabetes mellitus. SEARCH STRATEGY: Studies were obtained from computerised searches of multiple electronic databases and hand searches of reference lists of relevant trials identified. Date of last search: September 2003. SELECTION CRITERIA: Trials fulfilling the following inclusion criteria: Diabetes mellitus type 2, metformin versus any other oral intervention, assessment of relevant clinical outcome measures, use of random allocation. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data, using a standard data extraction form. Data were summarised under a random effects model. Dichotomous data were expressed as relative risk. We calculated the risk difference (RD), and the Number Needed to Treat, when it was possible. We collected data of mean and standard deviation from changes to baseline. However many trials reported end point data. This limitation lead to the expression of the results as standardised mean differences (SMD) and an overall SMD was calculated. Heterogeneity was tested for using the Z score and the I-squared statistic. Subgroup, sensitivity analysis and meta-regression were used to explore heterogeneity. MAIN RESULTS: We included for analysis 29 trials with 37 arms (5259 participants), comparing metformin (37 arms and 2007 participants) with sulphonylureas (13 and 1167), placebo (12 and 702), diet (three and 493), thiazolidinediones (three and 132), insulin (two and 439), meglitinides (two and 208), and glucosidase inhibitors (two and 111). Nine studies reported data on primary outcomes. Obese patients allocated to intensive blood glucose control with metformin showed a greater benefit than chlorpropamide, glibenclamide, or insulin for any diabetes-related outcomes (P = 0.009), and for all-cause mortality (P = 0.03). Obese participants assigned to intensive blood glucose control with metformin showed a greater benefit than overweight patients on conventional treatment for any diabetes-related outcomes (P = 0.004), diabetes-related death (P = 0.03), all-cause mortality (P = 0.01), and myocardial infarction (P = 0.02). Patients assigned to metformin monotherapy showed a significant benefit for glycaemia control, weight, dyslipidaemia, and diastolic blood pressure. Metformin presents a strong benefit for HbA1c when compared with placebo and diet; and a moderated benefit for: glycaemia control, LDL cholesterol, and BMI or weight when compared with sulphonylureas. AUTHORS' CONCLUSIONS: Metformin may be the first therapeutic option in the diabetes mellitus type 2 with overweight or obesity, as it may prevent some vascular complications, and mortality. Metformin produces beneficial changes in glycaemia control, and moderated in weight, lipids, insulinaemia and diastolic blood pressure. Sulphonylureas, alpha-glucosidase inhibitors, thiazolidinediones, meglitinides, insulin, and diet fail to show more benefit for glycaemia control, body weight, or lipids, than metformin.

Diabetes Mellitus, Type 2↗
PubMed2002

Blood transfusion for preventing stroke in people with sickle cell disease.

BACKGROUND: Sickle cell disease is a common inherited haemoglobin disorder. The abnormal haemoglobin causes distortion of red blood cells, anaemia, vaso-occlusion and dysfunction in virtually any organ system in the body. Stroke occurs in around 10% of children with sickle cell anaemia, and recurrences after a first stroke are likely. Chronic blood transfusion regimes are often used in an attempt to dilute the sickled red blood cells, thus reducing the risk of vaso-occlusion and stroke. However, the side-effects of such regimens can be severe. OBJECTIVES: To assess the relative risks and benefits of chronic blood transfusion regimes in patients with sickle cell disease to prevent a first stroke or further strokes. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's specialised register: July 2001 SELECTION CRITERIA: All those randomised or quasi-randomised controlled trials in which blood transfusion as a preventative measure for stroke in patients with sickle cell disease are compared to an alternative treatment or to no treatment. DATA COLLECTION AND ANALYSIS: Both reviewers independently assessed trial quality and extracted data from the study included. MAIN RESULTS: One trial was identified by the initial search and this met the inclusion criteria for the review. The trial compared a chronic transfusion regime to maintain sickle haemoglobin at less than 30% with standard care in 130 children with sickle cell disease who were judged to be at high risk of a first stroke through transcranial doppler ultrasonography. Eleven children in the standard care group suffered a stroke during the trial, compared to only one in the transfusion group. Because of this 92% relative risk reduction, the trial was terminated 16 months early. It had been planned that all patients would be treated for 30 months, but median follow-up only 21.1 months. However, a high rate of complications such as iron overload, alloimmunisation and transfusion reactions were seen in the children who were receiving transfusions. No randomised controlled trials were identified which investigated use of transfusion for preventing recurrence of stroke. REVIEWER'S CONCLUSIONS: While the included study demonstrated a significantly reduced risk of stroke in patients receiving regular blood transfusions, the degree of risk must be balanced against the burden of a chronic transfusion regime. Further research is required to establish the use of transfusion in preventing secondary stroke, the age, or length of time after an event, at which transfusion can safely be stopped, and to further define risk factors for stroke in order to reduce the chance of unnecessarily putting children onto a chronic transfusion regime.

Anemia, Sickle Cell↗
PubMed2004

Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis.

BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide constant back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect. OBJECTIVES: To determine the effectiveness and acceptability of PEP devices compared to other forms of physiotherapy as a means of improving mucus clearance and other outcomes in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register comprising of references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2001. Most recent search of the Group's register: November 2003. SELECTION CRITERIA: Randomised controlled trials in which PEP was compared with any other form of physiotherapy in people with CF. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion and exclusion criteria to publications and assessed the quality of the included studies. MAIN RESULTS: Thirty-three studies were identified and twenty studies involving 429 participants met review inclusion criteria. Most included studies had low scores on a scale of study quality. Sixteen of these studies involving 257 participants were cross-over in design. Data were not published in sufficient detail in these studies to perform meta-analysis.Forced expiratory volume in one second (FEV1) was the most frequently measured outcome. Single interventions or series of treatments continued for up to one month demonstrated no significant difference in effect between PEP and other methods of airway clearance on FEV1. Long-term studies had equivocal or conflicting results regarding the effect on FEV1. Patient preference was reported in nine studies. In all studies with an intervention period of at least one month, measures of patient preference were in favour of PEP. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high level evidence. REVIEWER'S CONCLUSIONS: There was no clear evidence that PEP was a more or less effective intervention overall than other forms of physiotherapy. There was limited evidence that PEP was preferred by participants compared to other techniques but this finding is from studies of low quality.

Cystic Fibrosis↗
PubMed2006

Positive expiratory pressure physiotherapy for airway clearance in people with cystic fibrosis.

BACKGROUND: Chest physiotherapy is widely prescribed to assist the clearance of airway secretions in people with cystic fibrosis (CF). Positive expiratory pressure (PEP) devices provide constant back pressure to the airways during expiration. This may improve clearance by building up gas behind mucus via collateral ventilation. Given the widespread use of PEP devices, there is a need to determine the evidence for their effect. OBJECTIVES: To determine the effectiveness and acceptability of PEP devices compared to other forms of physiotherapy as a means of improving mucus clearance and other outcomes in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The electronic database CINAHL was also searched from 1982 to 2001. Most recent search of the Group's register: February 2006. SELECTION CRITERIA: Randomised controlled studies in which PEP was compared with any other form of physiotherapy in people with CF. DATA COLLECTION AND ANALYSIS: Two authors independently applied the inclusion and exclusion criteria to publications and assessed the quality of the included studies. MAIN RESULTS: Forty studies were identified and twenty-five studies involving 507 participants met the review inclusion criteria. Most included studies had low scores on a scale of study quality. Twenty of these studies involving 300 participants were cross-over in design. Data were not published in sufficient detail in most of these studies to perform meta-analysis.Forced expiratory volume in one second (FEV1) was the most frequently measured outcome. Single interventions or series of treatments continued for up to three months demonstrated no significant difference in effect between PEP and other methods of airway clearance on FEV1. Long-term studies had equivocal or conflicting results regarding the effect on FEV1. Participant preference was reported in nine studies. In all studies with an intervention period of at least one month, measures of participant preference were in favour of PEP. The results for the remaining outcome measures were not examined or reported in sufficient detail to provide any high level evidence. AUTHORS' CONCLUSIONS: There was no clear evidence that PEP was a more or less effective intervention overall than other forms of physiotherapy. There was limited evidence that PEP was preferred by participants compared to other techniques, but this finding is from studies of low quality.

Cystic Fibrosis↗
PubMed2001

Preoperative blood transfusions for sickle cell disease.

BACKGROUND: Sickle cell disease is one of the most common inherited diseases in the world, and causes haemolytic anaemia, vaso-occlusive crises and dysfunction in virtually any organ system in the body. Surgical procedures are often required. Blood transfusion regimes can be used preoperatively in an attempt to increase transport of oxygen around the body and dilute the sickled red blood cells, thus reducing the risk of vaso-occlusion. OBJECTIVES: To assess the relative risks and benefits of preoperative blood transfusion regimes in patients with sickle cell disease undergoing surgery of any type in any setting. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search: January 2001 SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing preoperative blood transfusion regimes to different regimes or no transfusion in patients with sickle cell disease undergoing surgery. DATA COLLECTION AND ANALYSIS: Both reviewers independently assessed trial quality and extracted data from the study included. MAIN RESULTS: Only one trial met the inclusion criteria for the review. The trial compared an aggressive transfusion regime (decreasing sickle haemoglobin to less than 30%) to a conservative transfusion regime (increasing haemoglobin to 10 g/dl) in 604 elective operations in patients with sickle cell disease. The conservative regime was found to be as effective as the aggressive regime in preventing perioperative complications, and was associated with less transfusion related adverse events. No randomised controlled trials were found for transfusion compared to no transfusion. REVIEWER'S CONCLUSIONS: While in general conservative therapy appears to be as effective as aggressive in preparation for surgery in sickle cell patients, further research is needed to examine the optimal regime for different surgical types, and to address whether preoperative transfusion is needed in all surgical situations.

Anemia, Sickle Cell↗
PubMed2005

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 28 October 2004. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA an Nice and of companies' websites (Lundbeck, Merz, Forest, Suntori etc). SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. A major study (MD-01) is unpublished. Published data from two six month studies show a small beneficial effect of memantine at six months on cognition (4.12 SIB points, 95% Confidence Interval (CI) 2.14 to 5.74, P < 0.00001), activities of daily living (1.70 ADCS-ADLsev19 points, 95% CI 0.63 to 2.76, p = 0.002) and behaviour (3.64 NPI points, 95% CI 1.38 to 5.90, p = 0.002), supported by clinical impression of change (0.27 CIBIC+ points, 95% CI 0.10 to 0.43, p = 0.002). The unpublished study would need to have found a detrimental effect of memantine to overturn the statistical significance of the benefits apparent in the two published studies. 2. Mild to moderate AD. In a single six month trial, memantine had a beneficial effect on ITT analysis of cognition, (1.9 ADAS-Cog points, 95% CI 0.35 to 3.43, p = 0.02) and behaviour (3.50 NPI points 95% CI 0.15 to 6.85, p = 0.04) supported by clinical global impression of change (0.30 CIBIC+ points, 95% CI 0.09 to 0.51, p = 0.005), but no effect on activities of daily living or OC analysis of cognition. The statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect. 3. Mild to moderate vascular dementia. In two six month studies, memantine improved cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, p = 0.0002), and behaviour (Weighted Mean Difference (WMD) 0.84 95% CI 0.06 to 0.91, p = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine were less likely to develop agitation (Odds Ratio (OR): 0.65, 95% CI 0.48 to 0.89, p = 0.007). The effect on agitation which is already present is unknown.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Published data suggest a small beneficial effect of memantine at six months in moderate to severe AD. The beneficial effect on cognition in patients with mild to moderate vascular dementia was not clinically discernible at six months. Whether memantine has any effect in mild to moderate AD is unknown.

Activities of Daily Living↗
PubMed2005

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 20 May 2005. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (4.12 points on the 100 point SIB , 95% CI 2.14 to 5.74, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 NPI, 95% CI 0.88 to 4.63, P = 0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. In a single six month trial, memantine had a beneficial effect on ITT analysis of cognition, (1.9 ADAS-Cog points, 95% CI 0.35 to 3.45, P = 0.02) and behaviour (3.50 NPI points 95% CI 0.15 to 6.85, P = 0.04) supported by clinical global impression of change (0.30 CIBIC+ points, 95% CI 0.09 to 0.51, P = 0.005), but no effect on activities of daily living or OC analysis of cognition. The statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect. 3. Mild to moderate vascular dementia. In two six month studies, memantine improved cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine appeared to be less likely to develop agitation (93/1167 [8%] versus 134/1141 [12%] (Peto odds ratio (OR): 0.65, 95% CI 0.49 to 0.86, P = 0.002). This was consistently seen in moderate to severe dementia. There were no data which suggested an effect on agitation which is already present.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Published data suggest a small beneficial effect of memantine at six months in moderate to severe AD. The beneficial effect on cognition in patients with mild to moderate vascular dementia was not detectable on global assessment at six months. Whether memantine has any effect in mild to moderate AD is unknown.

Activities of Daily Living↗
PubMed2006

Memantine for dementia.

BACKGROUND: Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia. OBJECTIVES: To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia. SEARCH STRATEGY: The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 8th February 2006. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition, the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries. SELECTION CRITERIA: Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia. DATA COLLECTION AND ANALYSIS: Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported. MAIN RESULTS: 1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (2.97 points on the 100 point SIB, 95% CI 1.68 to 4.26, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 point NPI, 95% CI 0.88 to 4.63, P=0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001).2. Mild to moderate AD. Pooled data from three unpublished studies indicate a marginal beneficial effect at six months on ITT cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78, P = 0.01) which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25, P = 0.03) but no effect on behaviour, activities of daily living or OC analysis of cognition.3. Mild to moderate vascular dementia. Pooled data from two six month studies indicated a small beneficial effect of memantine on cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures.4. Patients taking memantine were slightly less likely to develop agitation (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04). This effect was slightly larger, but still small, in moderate to severe AD (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). There is no evidence either way about whether it has an effect on agitation which is already present.5. Memantine is well tolerated. AUTHORS' CONCLUSIONS: Memantine has a small beneficial effect at six months in moderate to severe AD. In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and was detectable in those with AD. Memantine is well tolerated.

Activities of Daily Living↗
PubMed2006

Interventions for vitiligo.

BACKGROUND: Around 1% of the world's population has vitiligo, which causes a loss of skin colour in patches. The methods currently available to treat vitiligo are largely unsatisfactory and vary widely between cultures and within health systems. OBJECTIVES: To assess the effects of interventions used to manage vitiligo. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, AMED and other databases (last searched September 2004). Reference lists of articles and conference proceedings were searched. Authors of reviews were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs). DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed study eligibility and methodological quality and carried out data extraction. The included studies compared different interventions and used different outcome measures so we considered it inappropriate to combine their results. MAIN RESULTS: Nineteen trials with a total of 1350 participants were included. The RCTs generally had low numbers of participants and only RCTs of repigmentation and not other methods of managing vitiligo were able to be included. In one study, potent topical steroids resulted in better repigmentation than placebo and they were also better than oral psoralens plus sunlight in another study (RR 4.70 95% CI 1.14 to 19.39) although their long-term use is limited by adverse effects. Two studies suggested that topical calcipotriol enhanced repigmentation rates from PUVAsol and PUVA when compared with placebo. Another two studies showed higher repigmentation rates with oral PUVAsol versus placebo plus sunlight (RR 19.20 95% CI 1.21 to 304.50 in 79 adults and RR 2.29 95% CI 1.14 to 4.58 in a study of 50 children). The safety of these interventions was poorly described and none of the studies was able to demonstrate long term benefits. Very few studies were carried out on children or included segmental vitiligo. No trials evaluating micropigmentation, melanocyte transplantation, depigmentation or cosmetic camouflage could be found. Despite the fact that the main impact of vitiligo is psychosocial only one study on psychological therapy was found and it is awaiting assessment. AUTHORS' CONCLUSIONS: This review has found some evidence to support existing therapies for vitiligo, but the different designs and outcome measurements, lack of quality of life measures and adverse effect reporting in the studies limit the usefulness of their findings. There is a pressing need for high quality randomised trials using standardised measures of repigmentation and which address relevant clinical outcomes including quality of life.

Humans↗
PubMed2006

Pharmacological management for agitation and aggression in people with acquired brain injury.

BACKGROUND: Of the many psychiatric symptoms that may result from brain injury, agitation and/or aggression are often the most troublesome. It is therefore important to evaluate the efficacy of psychotropic medication used in its management. OBJECTIVES: To evaluate the effects of drugs for agitation and/or aggression following acquired brain injury (ABI). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and other electronic databases. We also searched the reference lists of included studies and recent reviews. In addition we handsearched the journals Brain Injury and the Journal of Head Trauma Rehabilitation. There were no language restrictions. The searches were last updated in June 2006. SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the efficacy of drugs acting on the central nervous system for agitation and/or aggression, secondary to ABI, in participants over 10 years of age. DATA COLLECTION AND ANALYSIS: We independently extracted data and assessed trial quality. Studies of patients within six months after brain injury and/or in a confusional state, were distinguished from those of patients more than six months post-injury, or who were not confused. MAIN RESULTS: Six RCTs were identified and included in this review. Four of theses evaluated the beta-blockers, propranolol and pindolol, one evaluated the central nervous system stimulant, methylphenidate and one evaluated amantadine, a drug normally used in parkinsonism and related disorders. The best evidence of effectiveness in the management of agitation and/or aggression following ABI was for beta-blockers. Two RCTs found propranolol to be effective (one study early and one late after injury). However, these studies used relatively small numbers, have not been replicated, used large doses, and did not use a global outcome measure or long-term follow-up. Comparing early agitation to late aggression, there was no evidence for a differential drug response. Firm evidence that carbamazepine or valproate is effective in the management of agitation and/or aggression following ABI is lacking. AUTHORS' CONCLUSIONS: Numerous drugs have been tried in the management of aggression in ABI but without firm evidence of their efficacy. It is therefore important to choose drugs with few side effects and to monitor their effect. Beta-blockers have the best evidence for efficacy and deserve more attention. The lack of evidence highlights the need for better evaluations of drugs for this important problem.

Adrenergic beta-Antagonists↗
PubMed2003

Male circumcision for prevention of heterosexual acquisition of HIV in men.

BACKGROUND: The findings from observational studies, reviews and meta-analyses, supported by biological theories, that circumcised men appear less likely to acquire human immunodeficiency virus (HIV) has contributed to the recent ground swell of support for considering male circumcision as a strategy for preventing sexually acquired infection. We sought to elucidate and appraise the global evidence from published and unpublished studies that circumcision can be used as an intervention to prevent HIV infection. OBJECTIVES: 1) To assess the evidence of an interventional effect of male circumcision for preventing acquisition of HIV-1 and HIV-2 by men through heterosexual intercourse 2) To examine the feasibility and value of performing individual person data (IPD) meta-analysis SEARCH STRATEGY: We searched online for published and unpublished studies in The Cochrane Library (issue 2, 2002), MEDLINE (April 2002), EMBASE (February 2002) and AIDSLINE (August 2001). We also searched databases listing conference abstracts, scanned reference lists of articles and contacted authors of included studies. SELECTION CRITERIA: We searched for randomized and quasi-randomized controlled trials of male circumcision or, in their absence, observational studies that compare acquisition rates of HIV-1 and HIV-2 infection in circumcised and uncircumcised heterosexual men. DATA COLLECTION AND ANALYSIS: Independent reviewers selected studies, assessed study quality and extracted data. We stratified studies based on study design and on whether they included participants from the general population or high-risk groups (such as patients treated for sexually transmitted infections). We expressed findings as crude and adjusted odds ratios (OR) together with their 95% confidence intervals (CI) and conducted a sensitivity analysis to explore the effect of adjustment on study results. We investigated whether the method of circumcision ascertainment influenced study outcomes. MAIN RESULTS: We identified no completed randomized controlled trials. Three randomized controlled trials are currently underway or commencing shortly. We found 34 observational studies: 16 conducted in the general population and 18 in high-risk populations. It seems unlikely that potential confounding factors were completely accounted for in any of the included studies. In particular, important risk factors, such as religion and sexual practices, were not adequately accounted for in many of the included studies. General population study results:The single cohort study (N = 5516) showed a significant difference in HIV transmission rates between circumcised and uncircumcised men [OR = 0.58; 95% CI: 0.36 to 0.96]. Results for the 14 cross-sectional studies were inconsistent, with point estimates for unadjusted odds ratios varying between 0.28 and 1.73. Six studies had statistically significant results, four in the direction of benefit and two in the direction of harm. The test for heterogeneity between the cross-sectional studies was highly significant (chi-square = 77.59; df = 13; P-value < 0.00001). Nine studies reported adjusted odds ratios with eight in the direction of benefit, ranging from 0.26 to 0.80. Use of adjusted results tended to show stronger evidence of an association although they remained heterogenous (chi-square = 75.2; df = 13; P-value < 0.00001). Only one case-control study was found (N = 51) which had a non-significant result [OR = 1.90; 95% CI: 0.50 to 7.20]. High-risk group study results:The four cohort studies identified found a protective effect from circumcision with point estimates for unadjusted odds ratios varying from 0.10 to 0.39. Two of these studies had statistically significant results. Two studies reported adjusted odds ratios, both protective with one being significant. The chi-square test for between-study heterogeneity was not significant (chi-square = 5.21; df = 3; P-value = 0.16). All eleven cross-sectional studies reporting unadjusted results found benefit from circumcision, eight of which had statistically significant results. Estimates of effnal studies reporting unadjusted results found benefit from circumcision, eight of which had statistically significant results. Estimates of effect varied from an unadjusted odds ratio of 0.10 to 0.66. Between-study heterogeneity was significant with the chi-square = 29.77; df = 10; P-value = 0.0009. Four of these studies reported adjusted odds ratios ranging from 0.20 to 0.59 and all were significant. One additional cross-sectional study only reported an adjusted odds ratio in the direction of benefit which was statistically significant. All three case-control studies found a protective effect of circumcision on HIV status, two being statistically significant. Point estimates varied from unadjusted odds ratios of 0.37 to 0.88. One reported an adjusted odds ratio showing a significant protective effect. Adverse effects:No studies reported on the adverse effects of circumcision. In most studies, circumcision had taken place during childhood or adolescence before the studies commenced. REVIEWER'S CONCLUSIONS: We found insufficient evidence to support an interventional effect of male circumcision on HIV acquisition in heterosexual men. The results from existing observational studies show a strong epidemiological association between male circumcision and prevention of HIV, especially among high-risk groups. However, observational studies are inherently limited by confounding which is unlikely to be fully adjusted for. In the light of forthcoming results from RCTs, the value of IPD analysis of the included studies is doubtful. The results of these trials will need to be carefully considered before circumcision is implemented as a public health intervention for prevention of sexually transmitted HIV.

Circumcision, Male↗
PubMed2003

Drug therapies for reducing gastric acidity in people with cystic fibrosis.

BACKGROUND: Malabsorption of fat and protein contributes to the poor nutritional status in people with cystic fibrosis. Impaired pancreatic function may also result in increased gastric acidity leading in turn to heartburn, peptic ulcers and the impairment of oral pancreatic replacement therapy. The administration of gastric reducing agents has been used as an adjunct to pancreatic enzyme therapy to improve nutritional status, fat malabsorption and gastro-intestinal symptoms in people with cystic fibrosis. It is thus important to establish the current level of evidence regarding potential benefits of drug therapies that reduce gastric acidity in people with cystic fibrosis. OBJECTIVES: To assess the effect of drug therapies for reducing gastric acidity: in improving nutritional status; on symptoms associated with increased gastric acidity; fat absorption; lung function; quality of life and survival; and to determine if any adverse effects are associated with their use. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books and conference proceedings. Most recent search of the Group's register: April 2002. SELECTION CRITERIA: All randomised and quasi-randomised trials involving agents that reduce gastric acidity compared to placebo or a comparator treatment. DATA COLLECTION AND ANALYSIS: Both reviewers independently selected trials and assessed trial quality. MAIN RESULTS: Thirty-six trials were identified from the initial search. Eleven trials with 172 participants were suitable for inclusion. Five trials were limited to children and three trials enrolled only adults. One trial found that drug therapies which reduce gastric acidity improve gastro-intestinal symptoms such as abdominal pain. Five trials reported significant improvement in measures of fat malabsorption. Two trials reported no significant improvement in nutritional status. Only one trial reported measures of respiratory function and one trial reported an adverse effect with prostaglandin E2 analogue misoprostol. No trials have been identified which assess the effectiveness of agents that reduce gastric acidity in improving quality of life, the complications of increased gastric acidity, or survival. REVIEWER'S CONCLUSIONS: Trials have shown limited evidence that the agents which reduce gastric acidity in people with cystic fibrosis are associated with improvement in gastro-intestinal symptoms and fat absorption. Currently, there is insufficient evidence to indicate whether there is an improvement in nutritional status, lung function, quality of life, or survival. We therefore recommend large, multicentre, randomised controlled clinical trials are undertaken to evaluate these interventions.

Cystic Fibrosis↗
PubMed2002

Drugs for preventing red blood cell dehydration in people with sickle cell disease.

BACKGROUND: Sickle cell disease is an inherited disorder of haemoglobin, which results in abnormal red blood cells. These can deform and cause blockages in blood vessels, leading to acute crises such as pain, stroke and splenic sequestration, and chronic organ and tissue damage. Recently research has begun to focus on therapies which prevent the red blood cells deforming by reducing the loss of water and ions from the cells. However, little is known about the effectiveness and safety of such drugs. OBJECTIVES: To assess the relative risks and benefits of drugs which aim to prevent sickle cell related crises by reducing red blood cell dehydration. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search of the Group's specialised register: December 2001. SELECTION CRITERIA: All those randomised or quasi-randomised controlled trials of drugs which aim to prevent sickle cell crises by reducing red cell dehydration, compared to placebo or an alternative treatment. DATA COLLECTION AND ANALYSIS: Both reviewers independently selected trials for inclusion, assessed trial quality and extracted data from the included studies. MAIN RESULTS: Of the 27 trials identified, two met the inclusion criteria. The two trials tested the effectiveness of zinc sulphate and piracetam to prevent sickle cell related crises in a total of 246 patients. A reduction in pain crises was shown in the piracetam study over one year (weighted mean difference (WMD) -1.9 (95% CI -3.01, -0.79)), although blood counts were not significantly changed. The zinc trial showed a significant reduction in the total number of pain, haemolytic, aplastic and sequestration crises over one and a half years (WMD -2.83 (95% CI -3.51, -2.15)), but our analysis was limited by non-reporting of standard deviations for some data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in either trial. REVIEWER'S CONCLUSIONS: While the results of both zinc and piracetam for reducing sickle related crises are encouraging, larger, and/or longer term multicentre trials over a number of years are needed to evaluate the effectiveness of these therapies for patients with sickle cell disease.

Anemia, Sickle Cell↗
PubMed2002

Prophylactic antibiotics for preventing pneumococcal infection in children with sickle cell disease.

BACKGROUND: People with sickle cell disease are particularly susceptible to infection. Infants and very young children are especially vulnerable, and the Cooperative Study of Sickle Cell Disease observed an incidence rate of 10 per 100 patient years of pneumococcal septicaemia in children under the age of three. Vaccines, including customary pneumococcal vaccines, may be of limited use in this age group. Therefore, prophylactic penicillin regimes may be advisable for this population. OBJECTIVES: To assess the effects of prophylactic antibiotic regimes for preventing pneumococcal infection in children with sickle cell disease. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and hand searching abstract books of conference proceedings. Date of the most recent search: December 2001. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing prophylactic antibiotics to prevent pneumococcal infection in children with sickle cell disease with placebo, no treatment or a comparator drug. DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Five trials were identified by the initial search, of which three trials met the inclusion criteria. All of the included trials showed a reduced risk of infection in children with sickle cell disease (SS or Sb0Thal) receiving prophylactic penicillin. For initiation of treatment the odds ratio was 0.37 (95% CI 0.16, 0.86), and for withdrawal OR= 0.49 (95% CI 0.09, 2.71). Adverse drug effects were rare and minor. Rates of pneumococcal infection were found to be relatively low in children over the age of five. REVIEWER'S CONCLUSIONS: Prophylactic penicillin significantly reduces risk of pneumococcal infection in children with homozygous sickle cell disease, and is associated with minimal adverse reactions. Further research may help to determine the ideal age to safely withdraw penicillin.

Adolescent↗
PubMed2003

Parent-mediated early intervention for young children with autism spectrum disorder.

BACKGROUND: Recent estimates concerning the prevalence of autistic spectrum disorder are much higher than those reported 30 years ago, with at least 1 in 400 children affected. This group of children and families have important service needs. The involvement of parents in implementing intervention strategies designed to help their autistic children has long been accepted as helpful. The potential benefits are increased skills and reduced stress for parents as well as children. OBJECTIVES: The objective of this review was to determine the extent to which parent-mediated early intervention has been shown to be effective in the treatment of children aged 1 year to 6 years 11 months with autistic spectrum disorder. In particular, it aimed to assess the effectiveness of such interventions in terms of the benefits for both children and their parents. SEARCH STRATEGY: A range of psychological, educational and biomedical databases were searched. Bibliographies and reference lists of key articles were searched, field experts were contacted and key journals were hand searched. SELECTION CRITERIA: Only randomised or quasi-randomised studies were included. Study interventions had a significant focus on parent-implemented early intervention, compared to a group of children who received no treatment, a waiting list group or a different form of intervention. There was at least one objective, child related outcome measure. DATA COLLECTION AND ANALYSIS: Appraisal of the methodological quality of included studies was carried out independently by two reviewers. Differences between the included studies in terms of the type of intervention, the comparison groups used and the outcome measures were too great to allow for direct comparison. MAIN RESULTS: The results of this review are based on data from two studies. Two significant results were found to favour parent training in one study: child language and maternal knowledge of autism. In the other, intensive intervention (involving parents, but primarily delivered by professionals) was associated with better child outcomes on direct measurement than were found for parent-mediated early intervention, but no differences were found in relation to measures of parent and teacher perceptions of skills and behaviours. REVIEWER'S CONCLUSIONS: This review has little to offer in the way of implications for practice: there were only two studies, the numbers of participants included were small, and the two studies could not be compared directly to one another. In terms of research, randomised controlled trials involving large samples need to be carried out, involving both short and long-term outcome information and full economic evaluations. Research in this area is hampered by barriers to randomisation, such as availability of equivalent services.

Autistic Disorder↗
PubMed2004

Interventions for treating collagenous colitis.

BACKGROUND: Collagenous colitis is a disorder that is recognized as a cause of chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This review was performed to identify therapies for collagenous colitis that have been proven in randomized trials. OBJECTIVES: To determine effective treatments for patients with clinically active collagenous colitis. SEARCH STRATEGY: Relevant papers published between 1970 and August 2003 were identified via the MEDLINE and PUBMED databases. Manual searches from the references of identified papers, as well as review papers on collagenous or microscopic colitis were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Finally, the Cochrane Controlled Trials Register and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were searched for other studies. SELECTION CRITERIA: Five randomized trials were identified. One trial studied bismuth subsalicylate (published in abstract form only), one trial studied prednisolone, and 3 trials studied budesonide in the therapy of collagenous colitis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by each author onto 2x2 tables (treatment versus placebo and response versus no response). For therapies assessed in one trial only, p-values were derived using the chi-square test. For therapies assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. Data were combined for analysis only if the outcomes were sufficiently similar in definition. MAIN RESULTS: There were 9 patients with collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks). Those randomized to active drug were more likely to have clinical (p=0.003) and histological (p=0.003) improvement than those assigned to placebo. Eleven patients were enrolled in the trial studying prednisolone (50 mg daily for 2 weeks). There was a trend towards clinical response in patients on active medication compared to placebo (p=0.064). The effect of prednisolone on histologic improvement was not studied. A total of 94 patients were enrolled in 3 trials studying budesonide (9 mg daily or in a tapering schedule for 6 to 8 weeks). The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI 5.53-27.46), with a number needed to treat of 2 patients. There was significant histological improvement with treatment in all 3 trials studying budesonide therapy. REVIEWER'S CONCLUSIONS: Budesonide is effective for the treatment of collagenous colitis. The evidence for benefit with bismuth subsalicylate is weaker. Prednisolone may be effective for treatment of collagenous colitis, but only a single very small study has been reported. The effectiveness of these and other therapies for induction or maintenance of remission (as opposed to producing clinical or histological improvement) of collagenous colitis is unknown.

Anti-Inflammatory Agents↗
PubMed2005

Interventions for treating collagenous colitis.

BACKGROUND: Collagenous colitis is a disorder that is recognized as a cause of chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This review was performed to identify therapies for collagenous colitis that have been proven in randomized trials. OBJECTIVES: To determine effective treatments for patients with clinically active collagenous colitis. SEARCH STRATEGY: Relevant papers published between 1970 and June 2005 were identified via the MEDLINE and PUBMED databases. Manual searches from the references of identified papers, as well as review papers on collagenous or microscopic colitis were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Finally, the Cochrane Controlled Trials Register and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies. SELECTION CRITERIA: Six randomized trials were identified. One trial studied bismuth subsalicylate (published in abstract form only), one trial studied Boswellia serrata extract (published in abstract form only), one trial studied prednisolone, and 3 trials studied budesonide in the therapy of collagenous colitis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by each author onto 2x2 tables (treatment versus placebo and response versus no response). For therapies assessed in one trial only, p-values were derived using the chi-square test. For therapies assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. Data were combined for analysis only if the outcomes were sufficiently similar in definition. MAIN RESULTS: There were 9 patients with collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks). Those randomized to active drug were more likely to have clinical (p = 0.003) and histological (p = 0.003) improvement than those assigned to placebo. Eleven patients were enrolled in the trial studying prednisolone (50 mg daily for 2 weeks). There was a trend towards clinical response in patients on active medication compared to placebo (p = 0.064). The effect of prednisolone on histologic improvement was not studied. Thirty-one patients were enrolled in the Boswellia serrata extract trial. Clinical improvement was noted in 44% of patients who received active treatment compared to 27% of patients who received placebo (p = 0.32). A total of 94 patients were enrolled in 3 trials studying budesonide (9 mg daily or in a tapering schedule for 6 to 8 weeks). The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI 5.53 - 27.46), with a number needed to treat of 2 patients. There was significant histological improvement with treatment in all 3 trials studying budesonide therapy. Budesonide also appears to improve patients' quality of life. AUTHORS' CONCLUSIONS: Budesonide is effective for the treatment of collagenous colitis. The evidence for benefit with bismuth subsalicylate is weaker. The effectiveness of prednisolone and Boswellia serrata extract and other therapies for induction or maintenance of remission of collagenous colitis is unknown and requires further study.

Anti-Inflammatory Agents↗
PubMed2006

Interventions for treating collagenous colitis.

BACKGROUND: Collagenous colitis is a disorder that is recognized as a cause of chronic diarrhea. Treatment has been based mainly on anecdotal evidence. This review was performed to identify therapies for collagenous colitis that have been proven in randomized trials. OBJECTIVES: To determine effective treatments for patients with clinically active collagenous colitis. SEARCH STRATEGY: Relevant papers published between 1970 and June 2006 were identified via the MEDLINE and PUBMED databases. Manual searches from the references of identified papers, as well as review papers on collagenous or microscopic colitis were performed to identify additional studies. Abstracts from major gastroenterological meetings were searched to identify research submitted in abstract form only. Finally, the Cochrane Controlled Trials Register and the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Group Specialized Trials Register were searched for other studies. SELECTION CRITERIA: Seven randomized trials were identified. One trial studied bismuth subsalicylate (published in abstract form only), one trial studied Boswellia serrata extract (published in abstract form only), one trial studied probiotics, one trial studied prednisolone, and 3 trials studied budesonide for the therapy of collagenous colitis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by each author onto 2x2 tables (treatment versus placebo and response versus no response). For therapies assessed in one trial only, p-values were derived using the chi-square test. For therapies assessed in more than one trial, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. Data were combined for analysis only if the outcomes were sufficiently similar in definition. MAIN RESULTS: There were 9 patients with collagenous colitis in the trial studying bismuth subsalicylate (nine 262 mg tablets daily for 8 weeks). Those randomized to active drug were more likely to have clinical (p = 0.003) and histological (p = 0.003) improvement than those assigned to placebo. Eleven patients were enrolled in the trial studying prednisolone (50 mg daily for 2 weeks). There was a trend towards clinical response in patients on active medication compared to placebo (p = 0.064). The effect of prednisolone on histologic improvement was not studied. Thirty-one patients were enrolled in the Boswellia serrata extract trial. Clinical improvement was noted in 44% of patients who received active treatment compared to 27% of patients who received placebo (p = 0.32). Twenty-nine patients were enrolled in the probiotics trial. Clinical improvement was noted in 29% of patients who received probiotics compared to 13% of patients who received placebo (p = 0.635). A total of 94 patients were enrolled in 3 trials studying budesonide (9 mg daily or in a tapering schedule for 6 to 8 weeks). The pooled odds ratio for clinical response to treatment with budesonide was 12.32 (95% CI 5.53-27.46), with a number needed to treat of 2 patients. There was significant histological improvement with treatment in all 3 trials studying budesonide therapy. Budesonide also appears to improve patients' quality of life. AUTHORS' CONCLUSIONS: Budesonide is effective for the treatment of collagenous colitis. The evidence for benefit with bismuth subsalicylate is weaker. The effectiveness of prednisolone, Boswellia serrata extract, probiotics and other therapies for induction or maintenance of remission of collagenous colitis is unknown and requires further study.

Anti-Inflammatory Agents↗