Minoxidil for patchy alopecia areata: systematic review and meta-analysis.

BACKGROUND: Alopecia areata (AA) is a complex immune and polygenic inflammatory disease that causes hair loss on some or all areas of the body; extent, severity and progression vary widely among individuals. Alopecia areata, considered one of the most frequently occurring immune diseases, affects 0.2% of the world population at any given time. Uncertainty prevails about the most appropriate intervention for AA. The aim is to evaluate the effectiveness and safety of over 80 interventions for AA, including minoxidil - one of the most promising interventions for patchy AA in children and adults of both sexes. MATERIAL AND METHODS: An extensive search was conducted of international medical literature involving randomized clinical trials (RCTs) of AA interventions. RCTs were evaluated qualitatively and quantitatively according to the previously published protocol and for seven specific outcomes. RESULTS: The meta-analysis involving 5% minoxidil vs. placebo presented a significant difference in favor of 5% minoxidil with the moderate quality of evidence in children and adults with patchy AA (RR 8.37 [3.16-22.14], 95% CI). No severe adverse event was reported. CONCLUSIONS: Treatment of patchy AA with 5% minoxidil proved effective, and clinically and statistically safe in studies with limited sample size; quality of evidence was moderate. Further studies with sound methodological quality, more participants and outcome observations lasting longer than 6 months are needed to address remaining uncertainties.

Treatment for agenesis of maxillary lateral incisors: a systematic review.

OBJECTIVES: To compare the efficacy and safety of three orthodontic treatment modalities for agenesis of maxillary lateral incisors: 1) closing the space with the reshaped canine substituting the lateral incisor, 2) opening the space with placement of a conventional fixed bridge, and 3) opening the space with placement of a single-unit implant and an implant-supported crown. SETTING: Brazilian Cochrane Center and Universidade Federal de São Paulo, Brazil. MATERIAL AND METHODS: The following databases were investigated: Cochrane Register of Controlled Trials (Edition 12, 2011), EMBASE (from 1974 to December 2011), MEDLINE (from 1965 to December 2011), LILACS (from 1966 to November 2011), and Odontology Brazilian Bibliography Database (from 1966 to November 2011). Conference abstracts, main Brazilian dissertations and theses databases, and reference lists were handsearched. This systematic review included randomized or quasi-randomized controlled trials (RCTs) including women aged 15 years or over and men aged 21 years or over who received one of the interventions stated above. Two observers independently evaluated all the studies regarding eligibility criteria and assessed the risk of bias of included studies. RESULTS: No studies were included in the review as no RCTs were found. Most of the evidence comes from case reports and narrative reviews on case reports and from three studies with a single post-intervention evaluation and non-comparable control groups with high risk of bias. CONCLUSIONS: There is no scientific evidence for any of the three most common types of treatment for agenesis of the maxillary lateral incisors. RCTs into this issue are still necessary.

Vitamin C and superoxide dismutase (SOD) for diabetic retinopathy.

BACKGROUND: There is increasing evidence that diabetic retinopathy is caused by the action of free radicals. Radical scavengers like vitamin C and superoxide dismutase (SOD) may influence the outcome and progression of diabetic retinopathy, but no systematic review of the literature has been published to examine this hypothesis. OBJECTIVES: The aim of the current research was to review the literature in a standard systematic way in order to assess the effects of vitamin C and superoxide dismutase on diabetic retinopathy in methodologically robust trials. SEARCH STRATEGY: We tried to obtain studies from computerised searches of MEDLINE, EMBASE, CINAHL, Web of Science and The Cochrane Library. SELECTION CRITERIA: Only randomized clinical trials (RCTs) that evaluated the effect of vitamin C, superoxide dismutase or both in the treatment of diabetic retinopathy were considered. DATA COLLECTION AND ANALYSIS: Two authors independently read all abstracts, titles or both and wanted to assess risk of bias and to perform data extraction. Discrepancies were planned to be resolved by consensus or by the judgement of a third author. MAIN RESULTS: A total of 241 publications were identified by the electronic searches. Of these, 28 were identified as potentially containing information about the treatment of patients with diabetic retinopathy using vitamin C or SOD and were read in full. No trial evaluated the treatment of diabetic retinopathy with vitamin C or SOD. AUTHORS' CONCLUSIONS: No research to date has adequately examined the treatment of diabetic retinopathy with vitamin C or SOD in such a way as to indicate whether this form of intervention has a significant impact on the progress of this clinical condition. The potential role of these substances in the treatment of diabetic retinopathy remains open to debate, and it is suggested that future research focusing on patient-oriented outcomes should address this important issue.

Pentoxifylline for diabetic retinopathy.

BACKGROUND: There is increasing evidence that capillary occlusion plays an important part in the development of diabetic retinopathy. Disaggregants, such as pentoxyfilline may influence the outcome and progression of diabetic retinopathy, but no systematic review of the literature on its efficacy and safety has been published to examine this hypothesis. OBJECTIVES: The aim of the current research was to review the literature in a systematic way in order to assess the effects of pentoxyfilline for diabetic retinopathy in methodologically robust trials. The null hypothesis was that pentoxyfilline has no influence on the progression of diabetic retinopathy or blindness. SEARCH STRATEGY: A systematic search of electronic databases was carried out to identify publications. Relevant papers, written in any language, were accessed and assessed for data. SELECTION CRITERIA: Only randomized controlled clinical trials (RCTs) evaluating the effects of pentoxyfilline in the treatment of diabetic retinopathy were to be included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion criteria and for risk of bias. MAIN RESULTS: A total of 97 publications were identified by the electronic search and two authors checked the abstracts. Of these, 17 were identified as potentially relevant trials providing information about treatment of patients with diabetic retinopathy using pentoxyfilline and were read in full. Unfortunately, no publication fulfilled our inclusion criteria. AUTHORS' CONCLUSIONS: No sound research to date has examined the treatment of diabetic retinopathy with pentoxyfilline in such a way as to indicate whether this form of intervention has a significant impact on the natural history of this clinical condition. The potential role of this substance in the treatment of diabetic retinopathy remains open to debate, and it is suggested that future research focusing on patient-relevant outcomes takes the opportunity of addressing this important issue directly.

Zinc supplementation for the prevention of type 2 diabetes mellitus.

BACKGROUND: The chronic hyperglycaemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. The risk of developing type 2 diabetes increases with age, obesity, and lack of physical activity. Insulin resistance is a fundamental aspect of the aetiology of type 2 diabetes. Insulin resistance has been shown to be associated with atherosclerosis, hypertriglyceridaemia, glucose intolerance, dyslipidaemia, hyperuricaemia, hypertension and polycystic ovary syndrome. The mineral zinc plays a key role in the synthesis and action of insulin, both physiologically and in diabetes mellitus. Zinc seems to stimulate insulin action and insulin receptor tyrosine kinase activity. OBJECTIVES: To assess the effects of the zinc supplementation in the prevention of type 2 diabetes mellitus. SEARCH STRATEGY: Studies were obtained from computerised searches of MEDLINE, EMBASE, LILACS and The Cochrane Library. SELECTION CRITERIA: Studies were included if they had a randomised or quasi-randomised design and if they investigated zinc supplementation in adults living in the community, 18 years or older with insulin resistance (compared to placebo or no intervention). DATA COLLECTION AND ANALYSIS: Two authors selected relevant trials, assessed methodological quality and extracted data. MAIN RESULTS: Only one study met the inclusion criteria of this review. There were 56 normal glucose tolerant obese women (aged 25 to 45 years, body mass index 36.2 +/- 2.3 kg/m(2)). Follow-up was four weeks. The outcomes measured were decrease of insulin resistance, anthropometric and diet parameters, leptin and insulin concentration, zinc concentration in the plasma and urine, lipid metabolism and fasting plasma glucose. There were no statistically significant differences favouring participants receiving zinc supplementation compared to placebo concerning any outcome measured by the study. AUTHORS' CONCLUSIONS: There is currently no evidence to suggest the use of zinc supplementation in the prevention of type 2 diabetes mellitus. Future trials will have to standardise outcomes measures such as incidence of type 2 diabetes mellitus, decrease of the insulin resistance, quality of life, diabetic complications, all-cause mortality and costs.

Thyroid hormone replacement for subclinical hypothyroidism.

BACKGROUND: Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level with normal free thyroid hormones values. The prevalence of subclinical hypothyroidism is 4% to 8% in the general population, and up to 15% to 18% in women who are over 60 years of age. There is considerable controversy regarding the morbidity, the clinical significance of subclinical hypothyroidism and if these patients should be treated. OBJECTIVES: To assess the effects of thyroid hormone replacement for subclinical hypothyroidism. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE and LILACS. Ongoing trials databases, reference lists and abstracts of congresses were scrutinized as well. SELECTION CRITERIA: All studies had to be randomised controlled trials comparing thyroid hormone replacement with placebo or no treatment in adults with subclinical hypothyroidism. Minimum duration of follow-up was one month. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors for missing or additional information. MAIN RESULTS: Twelve trials of six to 14 months duration involving 350 people were included. Eleven trials investigated levothyroxine replacement with placebo, one study compared levothyroxine replacement with no treatment. We did not identify any trial that assessed (cardiovascular) mortality or morbidity. Seven studies evaluated symptoms, mood and quality of life with no statistically significant improvement. One study showed a statistically significant improvement in cognitive function. Six studies assessed serum lipids, there was a trend for reduction in some parameters following levothyroxine replacement. Some echocardiographic parameters improved after levothyroxine replacement therapy, like myocardial relaxation, as indicated by a significant prolongation of the isovolumic relaxation time as well as diastolic dysfunction. Only four studies reported adverse events with no statistically significant differences between groups. AUTHORS' CONCLUSIONS: In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups. Some evidence indicates that levothyroxine replacement improves some parameters of lipid profiles and left ventricular function.

Dipyrone for acute primary headaches.

BACKGROUND: Dipyrone is used to treat headaches in many countries, but is not available in others (particularly the USA and UK) because of its association with potentially life-threatening blood dyscrasias such as agranulocytosis. OBJECTIVES: To determine the effectiveness and safety of dipyrone for acute primary headaches in adults and children. SEARCH STRATEGY: We searched the Cochrane Pain, Palliative & Supportive Care Group's Trials Register; the Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; LILACS, and the reference lists of included studies. SELECTION CRITERIA: Double-blind randomised controlled trials of dipyrone for the symptomatic relief of acute primary headaches in adults and children. DATA COLLECTION AND ANALYSIS: Three authors independently screened articles, extracted data, assessed trial quality and analysed results. Relative risks (RRs), risk differences (RDs), weighted mean differences (WMDs), and numbers-needed-to-treat (NNTs) were calculated as appropriate. MAIN RESULTS: Four trials involving a total of 636 adult subjects were included. Methodological quality was generally high. One study each evaluated oral and intravenous dipyrone for episodic tension-type headache (ETTH); two trials evaluated intravenous dipyrone for migraine, but only one of these described pain outcomes. No pediatric trials were identified. The largest trial (n = 356) evaluated two doses (0.5 g, 1 g) of oral dipyrone for ETTH, which were significantly better than placebo for pain relief. The 1 g dose was also significantly better than acetylsalicylic acid (ASA) 1 g . A smaller trial (n = 60) evaluated intravenous dipyrone 1 g versus placebo for ETTH. RRs were statistically significant favouring dipyrone for pain-free and headache improvement outcomes. Finally, one trial (n = 134) evaluated intravenous dipyrone 1 g versus placebo for pain outcomes in patients with migraine. RRs were again statistically significant favouring dipyrone for pain-free and headache improvement outcomes. Two of the four trials assessed adverse events. No serious adverse events were reported, and no significant differences in adverse events were detected between dipyrone and comparators (placebo and ASA). AUTHORS' CONCLUSIONS: Evidence from a small number of trials suggests that dipyrone is effective for ETTH and migraine. No serious adverse events were observed in the included trials, but agranulocytosis is rare and would probably not be observed in such a relatively small sample. A study now ongoing in Latin America may clarify the true risk of agranulocytosis associated with dipyrone use.

Passiflora for anxiety disorder.

BACKGROUND: Anxiety is a very common mental health problem in the general population and in the primary care setting. Herbal medicines are popularly used worldwide and could be an option for treating anxiety if shown to be effective and safe. Passiflora (passionflower extract) is one of these compounds. OBJECTIVES: To investigate the effectiveness and safety of passiflora for treating any anxiety disorder. SEARCH STRATEGY: The following sources were used: electronic databases: Cochrane Collaboration Depression, Anxiety and Neurosis Cochrane Controlled Trials Register (CCDANCTR-Studies), Medline and Lilacs; Cross-checking references; contact with authors of included studies and manufacturers of passiflora. SELECTION CRITERIA: Relevant randomised and quasi-randomised controlled trials of passiflora using any dose, regime, or method of administration for people with any primary diagnosis of general anxiety disorder, anxiety neurosis, chronic anxiety status or any other mental health disorder in which anxiety is a core symptom (panic disorder, obsessive compulsive disorder, social phobia, agoraphobia, other types of phobia, postraumatic stress disorder). Effectiveness was measured using clinical outcome measures such as Hamilton Anxiety Scale (HAM-A) and other scales for anxiety symptoms. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials found through the search strategy, extracted data, performed the trial quality analyses and entered data. Where any disagreements occured, the third reviewer was consulted. Methodological quality of the trials included in this review was assessed using the criteria described in the Cochrane Handbook. For dichotomous outcomes, relative risk with 95% confidence intervals (CI) were calculated, and for continuous outcomes, weighted mean difference with 95%CI was used. MAIN RESULTS: Two studies, with a total of 198 participants, were eligible for inclusion in this review. Based on one study, a lack of difference in the efficacy of benzodiazepines and passiflora was indicated. Dropout rates were similar between the two interventions. Although the findings from one study suggested an improvement in job performance in favour of passiflora (post-hoc outcome) and one study showed a lower rate of drowsiness as a side effect with passiflora as compared with mexazolam, neither of these findings reached statistical significance. AUTHORS' CONCLUSIONS: RCTs examining the effectiveness of passiflora for anxiety are too few in number to permit any conclusions to be drawn. RCTs with larger samples that compare the effectiveness of passiflora with placebo and other types of medication, including antidepressants, are needed.

Incentive spirometry for preventing pulmonary complications after coronary artery bypass graft.

BACKGROUND: Following coronary artery bypass graft (CABG), the main causes of postoperative morbidity and mortality are postoperative pulmonary complications, respiratory dysfunction and arterial hypoxemia. Incentive spirometry is a treatment technique that uses a mechanical device (an incentive spirometer) to reduce such pulmonary complications during postoperative care. OBJECTIVES: To assess the effects of incentive spirometry for preventing postoperative pulmonary complications in adults undergoing CABG. SEARCH STRATEGY: We searched CENTRAL on The Cochrane Library (Issue 2, 2004), MEDLINE (1966 to December 2004), EMBASE (1980 to December 2004), LILACS (1982 to December 2004), the Physiotherapy Evidence Database (PEDro) (1980 to December 2004), Allied & Complementary Medicine (AMED) (1985 to December 2004), CINAHL (1982 to December 2004), and the Database of Abstracts of Reviews of Effects (DARE) (1994 to December 2004). References were checked and authors contacted. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials comparing incentive spirometry with any type of prophylactic physiotherapy for prevention of postoperative pulmonary complications in adults undergoing CABG. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated the quality of trials using the guidelines of the Cochrane Reviewers' Handbook and extracted data from included trials. MAIN RESULTS: Four trials with 443 participants contributed to this review. There was no significant difference in pulmonary complications (atelectasis and pneumonia) between treatment with incentive spirometry and treatment with positive pressure breathing techniques (continuous positive airway pressure (CPAP), bilevel positive airway pressure (BiPAP) and intermittent positive pressure breathing (IPPB)) or preoperative patient education. Patients treated with incentive spirometry had worse pulmonary function and arterial oxygenation compared with positive pressure breathing (CPAP, BiPAP, IPPB). AUTHORS' CONCLUSIONS: Individual small trials suggest that there is no evidence of benefit from incentive spirometry in reducing pulmonary complications and in decreasing the negative effects on pulmonary function in patients undergoing CABG. In view of the modest number of patients studied, methodological shortcomings and poor reporting of the included trials, these results should be interpreted cautiously. An appropriately powered trial of high methodological rigour is needed to determine those patients who may derive benefit from incentive spirometry following CABG.

Intermittent versus continuous androgen suppression for prostatic cancer.

BACKGROUND: After lung cancer, prostate cancer is the most common cause of death among males. The aim of treatment is to prevent disease-related morbidity and mortality while minimizing intervention-related adverse events. Androgen suppression therapy (AST) to reduce circulating serum testosterone and disease progression is considered a mainstay of treatment for men with advanced prostate cancer. It has been increasingly utilized for early stage disease despite a lack of evidence of effectiveness. OBJECTIVES: Evaluate the effectiveness and safety of intermittent androgen suppression (IAS) compared to continuous androgen suppression for treating prostatic cancer. SEARCH STRATEGY: The following databases were searched to identify randomised or quasi-randomised, controlled trials comparing intermittent and continuous androgen suppression in the treatment of any stage of prostate cancer: the Cochrane Central Register of Controlled Trials; EMBASE and LILACS. SELECTION CRITERIA: Studies were included if they were randomised or quasi-randomized, and compare the effects of IAS versus CAS. DATA COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed methodological quality and extracted data. MAIN RESULTS: Five randomized studies involving 1382 patients were included in this review. All the included studies involved advanced (T3 or T4) prostate cancer, had relatively small populations, and were of short duration. Few events were reported and did not assess disease-specific survival or metastatic disease. Only one study (N = 77) evaluated biochemical outcomes. A subgroup analysis found no significant differences in biochemical progression (defined by the authors as PSA >/= 10 ng/mL) between IAS and CAS for Gleason scores 4 - 6, 7, and 8 - 10. For patients with a Gleason score > 6, reduction in biochemical progression favoured the IAS group (RR 0.10, 95% CI 0.01 to 0.67, P = 0.02). Studies primarily reported on adverse events. One trial (N = 43) found no difference in adverse effects (gastrointestinal, gynecomastia and asthenia) between IAS ( two events) and CAS (five events), with the exception of impotence, which was significantly lower in the IAS group (RR 0.72, 95% CI 0.56 to 0.92, P = 0.008). AUTHORS' CONCLUSIONS: Data from RCTs comparing IAS to CAS are limited by small sample size and short duration. There are no data for the relative effectiveness of IAS versus CAS for overall survival, prostate cancer-specific survival, or disease progression. Limited information suggests IAS may have slightly reduced adverse events. Overall, IAS was also as effective as CAS for potency, but was superior during the interval of cycles (96%).

Intragastric balloon for obesity.

BACKGROUND: Obesity is one of the major public health problems of modern society. Intragastric balloon (IGB) treatment for obesity has been developed as a temporary aid. Its primary objective is the treatment of obese people, who have had unsatisfactory results in their clinical treatment for obesity, despite of being cared for by a multidisciplinary team, and super obese patients with a higher surgical risk. However, the effects of different IGB procedures compared with conventional treatments and with each other are uncertain. OBJECTIVES: To assess the effects of intragastric balloon in people with obesity. SEARCH STRATEGY: Studies were obtained from computerised searches of MEDLINE, EMBASE, LILACS, The Cochrane Library and other electronic databases. Furthermore, reference lists of relevant articles and hand searches of selected journals were performed. Experts in the field were contacted. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials fulfilling the inclusion criteria were used. Short term weight loss is common, so studies were included if they reported measurements after a minimum of four weeks follow-up. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked independently by two reviewers. Two reviewers independently assessed the quality of trials. MAIN RESULTS: Nine randomised controlled trials involving 395 patients were included. Six out of nine studies had a follow-up of less than one year, the longest study duration was 24 months. Only a third of the analysed studies revealed a low risk of bias. No information was available on quality of life, all-cause mortality and morbidity. Compared with conventional management, IGB did not show convincing evidence of a greater weight loss. On the other hand, complications of intragastric balloon placement occurred, however few of a serious nature. The relative risks for minor complications like gastric ulcers and erosions were significantly raised. AUTHORS' CONCLUSIONS: Evidence from this review is limited for decision making, since there was large heterogeneity in IGB trials, regarding both methodological and clinical aspects. However, a co-adjuvant factor described by some authors in the loss and maintenance of weight has been the motivation and the encouragement to changing eating habits following a well-organized diet and a program of behavioural modification. The IGB alone and the technique of positioning appear to be safe. Despite the evidence for little additional benefit of the intragastric balloon in the loss of weight, its cost should be considered against a program of eating and behavioural modification.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia through a number of mechanisms, and may help to prevent preterm labour. OBJECTIVES: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2005, Issue 4), and contacted study authors. SELECTION CRITERIA: Randomised trials comparing at least one gram daily of calcium during pregnancy with placebo. DATA COLLECTION AND ANALYSIS: We assessed eligibility and trial quality, extracted and double-entered data. MAIN RESULTS: Twelve studies of good quality were included. The risk of high blood pressure was reduced with calcium supplementation rather than placebo (11 trials, 14,946 women: relative risk (RR) 0.70, 95% confidence interval (CI) 0.57 to 0.86). There was also a reduction in the risk of pre-eclampsia associated with calcium supplementation (12 trials, 15,206 women: RR 0.48, 95% CI 0.33 to 0.69). The effect was greatest for high-risk women (5 trials, 587 women: RR 0.22, 95% CI 0.12 to 0.42), and those with low baseline calcium intake (7 trials, 10,154 women: RR 0.36, 95% CI 0.18 to 0.70). The composite outcome maternal death or serious morbidity was reduced (4 trials, 9732 women; RR 0.80, 0.65 to 0.97). Almost all the women in these trials were low risk and had a low calcium diet. Maternal deaths were reported in only one trial. One death occurred in the calcium group and six in the placebo group, a difference which was not statistically significant (RR 0.17, 95% CI 0.02 to 1.39). There was no overall effect on the risk of preterm birth (10 trials, 14,751 women: RR 0.81, 95% CI 0.64 to 1.03), or stillbirth or death before discharge from hospital (10 trials 15,141 babies; RR 0.89, 95% CI 0.73 to 1.09).Blood pressure in childhood has been assessed in one study: childhood systolic blood pressure greater than 95th percentile was reduced (514 children: RR 0.59, 95% CI 0.39 to 0.91). AUTHORS' CONCLUSIONS: Calcium supplementation appears to almost halve the risk of pre-eclampsia, and to reduce the rare occurrence of the composite outcome 'death or serious morbidity'. There were no other clear benefits, or harms.

Valerian for anxiety disorders.

BACKGROUND: Anxiety disorders are very common mental health problems in the general population and in primary care settings. Herbal medicines are popular and used worldwide and might be considered as a treatment option for anxiety if shown to be effective and safe. OBJECTIVES: To investigate the effectiveness and safety of valerian for treating anxiety disorders. SEARCH STRATEGY: Electronic searches: The Cochrane Collaboration Depression, Anxiety and Neurosis Cochrane Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) searched on 04/08/2006, MEDLINE, Lilacs. References of all identified studies were inspected for additional studies. First authors of each included study, manufacturers of valerian products, and experts in the field were contacted for information regarding unpublished trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials of valerian extract of any dose, regime, or method of administration, for people with any primary diagnosis of general anxiety disorder, anxiety neurosis, chronic anxiety status, or any other disorder in which anxiety is the primary symptom (panic disorder, obsessive compulsive disorder, social phobia, agoraphobia, other types of phobia, postraumatic stress disorder). Effectiveness was measured using clinical outcome measures and other scales for anxiety symptoms. DATA COLLECTION AND ANALYSIS: Two review authors independently applied inclusion criteria, extracted and entered data, and performed the trial quality assessments. Where disagreements occurred, the third review author was consulted. Methodological quality of included trials was assessed using Cochrane Handbook criteria. For dichotomous outcomes, relative risk (RR) was calculated, and for continuous outcomes, the weighted mean difference (WMD) was calculated, with their respective 95% confidence intervals. MAIN RESULTS: One RCT involving 36 patients wih generalised anxiety disorder was eligible for inclusion. This was a 4 week pilot study of valerian, diazepam and placebo. There were no significant differences between the valerian and placebo groups in HAM-A total scores, or in somatic and psychic factor scores. Similarly, there were no significant differences in HAM-A scores between the valerian and diazepam groups, although based on STAI-Trait scores, significantly greater symptom improvement was indicated in the diazepam group. There were no significant differences between the three groups in the number of patients reporting side effects or in dropout rates. AUTHORS' CONCLUSIONS: Since only one small study is currently available, there is insufficient evidence to draw any conclusions about the efficacy or safety of valerian compared with placebo or diazepam for anxiety disorders. RCTs involving larger samples and comparing valerian with placebo or other interventions used to treat of anxiety disorders, such as antidepressants, are needed.

Interventions to promote the wearing of hearing protection.

BACKGROUND: Noise induced hearing loss can only be prevented by eliminating or lowering noise exposure levels. Where the source of the noise can not be eliminated workers have to rely on hearing protective equipment. Several trials have been conducted to study the effectiveness of interventions to influence the wearing of hearing protection and to decrease noise exposure. We aimed to establish whether interventions to increase the wearing of hearing protection are effective. OBJECTIVES: To summarise the evidence for the effectiveness of interventions to enhance the wearing of hearing protection among workers exposed to noise in the workplace. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2 2005), MEDLINE (1966 to June 2005), EMBASE (1980 to June 2005), NIOSHTIC, CISDOC, CINAHL, LILACS (1982 to June 2005) and Scientific Electronic Library Online. The date of the last search was June 2005. SELECTION CRITERIA: Studies were included if they had a randomised design, if they were among noise exposed (> 80 dB(A)) workers or pupils, if there was some kind of intervention to promote the wearing of hearing protection (compared to another intervention or no intervention), and if the outcome measured was the amount of use of hearing protection or a proxy measure thereof. DATA COLLECTION AND ANALYSIS: Two reviewers selected relevant trials, assessed methodological quality and extracted data. There were no cases where the pooling of data was appropriate. MAIN RESULTS: Two studies were found. One study was a two-phased randomised controlled trial. A computer-based intervention tailored to the risk of an individual worker lasting 30 minutes was not found to be more effective than a video providing general information among workers, around 80% of whom already used hearing protection. The second phase of the trial involved sending a reminder to the home address of participants at 30 days, 90 days or at both 30 and 90 days after the intervention, or no reminder. No significant differences in the mean use of hearing protection were found. A second randomised controlled trial evaluated the effect of a four year school based hearing loss prevention programme among pupils working at their parents farms (N=753) in a cluster randomised controlled trial. The intervention group was twice as likely to wear some kind of hearing protection as the control group that received only minimal intervention. All results are based on self reported use of hearing protection. AUTHORS' CONCLUSIONS: Limited evidence does not show whether tailored interventions are more or less effective than general interventions in workers, 80% of whom already use hearing protection. Long lasting school based interventions may increase the use of hearing protection substantially. These results are based on single studies only. Better interventions to enhance the use of hearing protection need to be developed and evaluated in order to increase the prevention of noise induced hearing loss among workers.

Cyclophosphamide versus methylprednisolone for treating neuropsychiatric involvement in systemic lupus erythematosus.

BACKGROUND: Neuropsychiatric involvement in systemic lupus erythematosus is complex and several clinical presentations are related to this disease such as: convulsions, chronic headache, transverse myelitis, vascular brain disease, psychosis and neural cognitive dysfunction. This systematic review is an update of a review performed in 2000. OBJECTIVES: To assess the efficacy and safety of cyclophosphamide and methylprednisolone in the treatment of neuropsychiatric manifestations of systemic lupus erythematosus. SEARCH STRATEGY: We searched EMBASE, LILACS, Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE up to and including May 2005. Additional articles were sought through handsearching in relevant journals. There were no language restrictions. SELECTION CRITERIA: All randomised controlled trials that compared cyclophosphamide to methylprednisolone were included. Patients of any age and gender were included as long as they fulfilled the criterion of the American College of Rheumatology for the diagnosis of systemic lupus erythematosus and presented with any one of the following neuropsychiatric events: convulsions, organic brain syndrome and cranial neuropathy. Outcome measures included the following: a) overall mortality (primary event); b) motor and psychiatric deficit (primary event); c) clinical improvement (secondary event). DATA COLLECTION AND ANALYSIS: Data was independently extracted by two reviewers and cross-checked. The methodological quality of each trial was assessed by the same two reviewers. Details of the randomisation (generation and concealment), blinding, and the number of patients lost to follow-up were recorded. Dichotomous data was presented as relative risks with corresponding 95% confidence intervals and a clinical relevance table was produced. MAIN RESULTS: We found one randomised controlled trial of 32 patients comparing cyclophosphamide versus methylprednisolone for the treatment of neuropsychiatric involvement in the systemic lupus erythematosus. A significantly greater number of people responded to treatment in the cyclophosphamide group. Treatment response was found in 94.7% (18/19) of patients using cyclophosphamide compared with 46.2% (6/13) in the methylprednisolone group at 24 months (RR 2.05, 95% CI 1.13, 3.73) The NNT for response to treatment is 2. Cyclophosphamide use was associated with a reduction in prednisone requirements. A significant decrease in the number seizures per month was observed in the cyclophosphamide group. All the patients in the cyclophosphamide group had electroencephalographic improvement. No significant differences in adverse effects between the groups were found. It was not possible to extract more data from the study because there was a small number of patients in the others clinical subgroups of neurological manifestations and the authors did not provide sufficient information for data extraction. AUTHORS' CONCLUSIONS: This systematic review found one randomised controlled trial with a small number of patients in the different clinical subgroups of neurological manifestation. It seems that cyclophosphamide is more effective in the treatment of neuropsychiatric involvement in systemic erythematosus lupus compared with methylprednisolone. However, properly designed randomised controlled trials that involve large, representative numbers of individuals, with explicit clinical and laboratory diagnosis criteria, sufficient duration of follow-up and description of all relevant outcome measures are necessary to guide practice.

Mechanical bowel preparation for elective colorectal surgery.

BACKGROUND: For over a century the presence of bowel content during surgery has been linked to anastomotic leakage. Mechanical bowel preparation has been considered an efficient agent against leakage and infectious complications. This dogma is not based on solid evidence, but on observational data and expert's opinions. OBJECTIVES: To determine the effectiveness and safety of prophylactic mechanical bowel preparation for morbidity and mortality rates in elective colorectal surgery. SEARCH STRATEGY: We searched MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials. We also searched relevant medical journals, and conference proceedings from major gastroenterological congresses and contacted experts in the field. We used the search strategy described by the Colorectal Cancer Review Group, without limitations for date of publication and language. I SELECTION CRITERIA: Randomised, clinical trials that compared any strategy in mechanical bowel preparation with no mechanical bowel preparation. DATA COLLECTION AND ANALYSIS: Data were independently extracted by the reviewers and cross-checked. The same reviewers assessed the methodological quality of each trial. Details of the randomisation (generation and concealment), blinding, whether an intention-to-treat analysis was done, and the number of patients lost to follow-up was recorded. For analysis the Peto odds ratio (OR) was used as defaults. MAIN RESULTS: Of the 1592 patients (9 trials), 789 were allocated to mechanical bowel preparation (Group A) and 803 to no preparation (Group B) before elective colorectal surgery. For anastomotic leakage (main outcome) the results were: - Low anterior resection: 9.8% (11 of 112 patients in Group A) compared with 7.5% (9 of 119 patients in Group B); Peto OR 1.45, 95% confidence interval (CI): 0.57 to 3.67 (non-significant); - Colonic surgery: 2.9% (Group A) compared with 1.6% (Group B) ; Peto OR 1.80, 95% CI: 0.68 to 4.75 (non-significant); Overall anastomotic leakage: 6.2% (Group A) compared with 3.2% (Group B); Peto OR 2.03, 95% CI: 1.276 to 3.26 (p=0.003). For the secondary outcome of wound infection the result was: 7.4% (Group A) compared with 5.4% (Group B); Peto OR 1.46, 95% CI: 0.97 - to 2.18 (p=0.07); Sensitivity analyses excluding studies with dubious randomisation, studies published as abstracts only, and studies involving children did not change the overall conclusions AUTHORS' CONCLUSIONS: There is no convincing evidence that mechanical bowel preparation is associated with reduced rates of anastomotic leakage after elective colorectal surgery. On the contrary, there is evidence that this intervention may be associated with an increased rate of anastomotic leakage and wound complications. It is not possible to be conclusion on the latter issue because of the clinical heterogeneity of trial inclusion criteria, methodological inadequacies in trial (in particular, poor reporting of concealment and allocation), potential performance biases, and failure of intention-to-treat analyses. Nevertheless, the dogma that mechanical bowel preparation is necessary before elective colorectal surgery should be reconsidered.

Interventions for treating posterior cruciate ligament injuries of the knee in adults.

BACKGROUND: Injuries of the posterior cruciate ligament (PCL) of the knee frequently occur in automobile accidents and sports injuries, although they are less frequent overall than injuries of the anterior cruciate ligament (ACL). Some patients show significant symptoms and subsequent articular deterioration, while others are essentially asymptomatic, maintaining habitual function. Management of PCL injuries remains controversial and prognosis can vary widely. Interventions extend from non-operative (conservative) procedures to reconstruction of the PCL, in the hope that the surgical procedure may have a positive effect in the reduction/prevention of future osteoarthritic changes in the knee. OBJECTIVES: To determine the effectiveness and safety of surgical and conservative interventions for PCL injuries in adults. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group Specialised Register (April 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2004), MEDLINE via PubMed (1966 to April 2004), EMBASE (1966 to April 2004), CINAHL (1982 to April 2004), LILACS (1982 to April 2004), SportsDiscus (1975 to April 2004), and reference lists of articles. SELECTION CRITERIA: Randomized or quasi-randomized clinical trials comparing various methods of operative and conservative interventions, and comparisons with each other for the treatment of PCL injuries. DATA COLLECTION AND ANALYSIS: References found with the search strategy were evaluated independently by two review authors. MAIN RESULTS: No randomized or quasi-randomized controlled studies meeting the selection criteria were identified. AUTHORS' CONCLUSIONS: Future research should include randomized controlled trials of acute isolated PCL injuries, or PCL injuries when combined with other ligament injuries of the knee, treated operatively and conservatively. Adequate numbers of patients and an objective methodology for patient evaluation must be used in future studies of these interventions to determine the long-term results.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Calcium supplementation may prevent high blood pressure through a number of mechanisms and may help to prevent preterm labour. OBJECTIVES: The objective of this review was to assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child adverse outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register and we contacted study authors. SELECTION CRITERIA: Randomised trials comparing at least one gram daily of calcium during pregnancy compared to placebo. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed. Data extraction was carried out independently by two reviewers. MAIN RESULTS: Nine studies were included, all of good quality. There was a modest reduction in high blood pressure with calcium supplementation (relative risk 0.80, 95% confidence interval 0.73 to 0.88). The effect was greatest for women at high risk of hypertension (relative risk 0.35, 95% confidence interval 0.21 to 0.57) and those with low baseline dietary calcium (relative risk 0.49, 95% confidence interval 0.38 to 0.62). There was also a modest reduction in the risk of pre-eclampsia with calcium supplementation (relative risk 0. 72, 95% confidence interval 0.60 to 0.86). The effect was greatest for women at high risk of hypertension (relative risk 0.22, 95% confidence interval 0.11 to 0.43) and those with low baseline calcium intake (relative risk 0.32, 95% confidence interval 0.21 to 0.49). There was no overall effect on the risk of preterm delivery, although there was a reduction in risk amongst women at high risk of hypertension (relative risk 0.42, 95% confidence interval 0.23 to 0. 78). There was no evidence of any effect of calcium supplementation on stillbirth or death before discharge from hospital. REVIEWER'S CONCLUSIONS: Calcium supplementation appears to be beneficial for women at high risk of gestational hypertension and in communities with low dietary calcium intake. Optimum dosage requires further investigation.

Antibiotics for treating leptospirosis.

BACKGROUND: Leptospirosis is a parasitic disease transmitted by animals. Severe leptospirosis may result in hospitalisation and about five per cent of the patients die. In clinical practice, penicillin is widely used for treating leptospirosis. OBJECTIVES: To evaluate the effectiveness and safety of antibiotics versus placebo or other antibiotic regimens in treating leptospirosis. We addressed the following clinical questions: a) Are treatment regimens with antibiotics more efficient than placebo for leptospirosis? b) Are treatment regimens with antibiotics safe when compared to placebo for leptospirosis? c) Which antibiotic regimen is the most efficient and safest in treating leptospirosis? SEARCH STRATEGY: Electronic searches and searches of the identified articles were combined. STUDIES: Randomised clinical trials in which antibiotics were used as treatment for leptospirosis. Language, date, or other restrictions were not applied. PARTICIPANTS: Patients with clinical manifestations of leptospirosis. INTERVENTIONS: Any antibiotic regimen compared with a control group (placebo or another antibiotic regimen). DATA COLLECTION AND ANALYSIS: Data and methodological quality of each trial were independently extracted and assessed by two reviewers. The random effects model was used irrespective of significant statistical heterogeneity. MAIN RESULTS: Three trials met inclusion criteria. Allocation concealment and double blind methods were not clearly described in two. Of the patients enrolled, 75 were treated with placebo and 75 with antibiotics: 61 (81.3%) penicillin and 14 (18.6%) doxycycline. The patients assigned to antibiotics compared to placebo showed: a) Mortality: 1% (1/75) versus 4% (3/75); risk difference -2%, 95% confidence interval -8% to 4%. b) Duration of hospital stay (days): weighted mean difference 0.30, 95% confidence interval -1.26 to 1.86. c) Prolonged hospital stay (> seven days): 30% (7/23) versus 74% (14/19); risk difference -43%, 95% confidence interval -70% to -16%. Number needed-to-treat 3, 95% confidence interval 2 to 7. d) Period of disappearance of fever (days): weighted mean difference -4.04, 95% confidence interval -8.65 to 0.58. e) Leptospiruria: 5% (4/75) versus 40% (30/75); risk difference -46%, 95% confidence interval -88% to -3%. Number needed-to-treat 2, 95% confidence interval 1 to 33. REVIEWER'S CONCLUSIONS: Antibiotic regimens for treatment of leptospirosis is a form of care for which the evidence is insufficient to provide clear guidelines for practice. The randomised trials suggest that antibiotics could be a useful treatment for leptospirosis. Because of the questionable quality of two of the three trials, the indication for general use of antibiotics is uncertain. However, the evidence suggest that penicillin may cause more good than harm.